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PubMed1995

Pathology of subcortical visual centres in relation to cortical degeneration in Alzheimer's disease.

Subcortical visual centres such as the lateral geniculate nucleus, the lateral inferior pulvinar and the superior colliculus, together with the primary visual cortex and its adjacent white matter, were studied in 12 Alzheimer brains and five age-matched controls. The periodic acid methenamine technique was used for the demonstration of senile plaques and the Gallyas technique for neurofibrillary tangles and neuritic threads in the neuropil. In the lateral geniculate nucleus and inferior pulvinar, the presence of periodic acid methenamine-positive senile plaques was observed in variable numbers in all Alzheimer cases. In the lateral geniculate nucleus, senile plaques were encountered more often in parvocellular than in magnocellular layers, in the interlaminar zones, in the optic radiation and in the adjacent pre-geniculate nucleus. Gallyas staining did not reveal any neurofibrillary tangles, neuritic threads or neuritic plaques, meaning that in this thalamic region there are mainly amyloid deposits without neuritic degeneration. In the superior colliculus both amyloid and neuritic plaques, as well as neurofibrillary tangles and neuritic threads were encountered in the superficial and deep layers. In the primary visual cortex, all types of senile plaques were observed as well as a rather high number of neurofibrillary lesions in pyramidal neurons, mainly in layers 5 and 6, but also in several types of non-pyramidal neurons. In the underlying white matter there was a morphologically heterogeneous population of neurofibrillary tangle-bearing neurons and a considerable number of threads representing degenerating axons, suggesting that degeneration could follow corticosubcortical connections. These data demonstrate that lesions in the primary visual structures and pathways are more prevalent than previously observed and could partly explain the visual disturbances in Alzheimer's disease.

Aged↗
PubMed2001

Progressive supranuclear palsy: clinical features, pathophysiology and management.

Progressive supranuclear palsy (PSP) is a degenerative condition of unknown aetiology that produces an akinetic-rigid form of parkinsonism characterised by early falls and abnormalities of extraocular movements. Mean age of onset is approximately 63 years, and mean survival from symptom onset is 9 years. Men are much more frequently affected than women. The classic clinical finding is supranuclear ophthalmoplegia, which may not present until late in the illness, if at all. The clinical diagnosis of PSP can be difficult to make, as the sites of pathology are heterogeneous. Structural and functional neuroimaging studies, although not specific for PSP, may be of some assistance in making the diagnosis. The definitive diagnosis of PSP requires the presence of both clinical and neuropathological evidence. Multiple anatomical sites are affected in PSP. The most consistently involved are the subthalamic nucleus, globus pallidus interna and externa, pontine nuclei, periaqueductal grey matter and the substantia nigra. The location of the pathology accounts for the clinical features. The histological hallmark of PSP is the presence of globose neurofibrillary tangles in the affected subcortical nuclei. Neurofibrillary tangles are composed of abnormally phosphorylated tau, a microtubule-associated protein that is involved in maintenance of the cytoskeleton. Abnormalities near or in the gene coding for tau are implicated in the pathogenesis of PSP. The multiple neurotransmitter abnormalities, including those affecting dopamine, acetylcholine, gamma-aminobutyric acid and norepinephrine (noradrenaline) systems and pathways, as well as both pre- and post-synaptic pathology, make pharmacological therapy of PSP a challenge. Although an individual patient may respond to a drug, in general patients with PSP have a minimal response and a short duration of sustained benefit.

Animals↗
PubMed2005

Altered p59Fyn kinase expression accompanies disease progression in Alzheimer's disease: implications for its functional role.

Alzheimer's disease (AD) is characterized by progressive decline in memory and other cognitive domains, accompanied by early loss of presynaptic terminals, amyloid-bearing neuritic plaques and neurofibrillary tangles containing hyperphosphorylated tau. The mechanisms leading to neurodegeneration are not completely understood, however, recent evidence suggests that alterations in p59Fyn kinase, an Src family tyrosine kinase, might contribute to AD pathogenesis. In this context, the main objective of the present study was to investigate the relationship between Fyn protein levels and the neurological and neuropathological alterations in AD. We found, by quantitative immunoblotting, that in AD, Fyn levels were increased in the insoluble fraction and decreased in the soluble fraction. Soluble Fyn levels were directly correlated with the cognitive scores and levels of synaptophysin immunoreactivity, and inversely correlated with neurofibrillary tangle counts in the frontal cortex. Consistent with these findings, the immunocytochemical analysis showed that in AD cases, Fyn levels were decreased in the synapses and increased in the neuronal cell bodies where it was colocalized with neurofibrillary tangles. Taken together, these findings suggest that alterations in Fyn localization might be associated with neurofibrillary pathology and synapse loss in AD.

Aged↗
PubMed2006

LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?

The presence of alpha-synuclein Lewy body pathology is used to distinguish Parkinson's disease from parkinsonism, for which a broader spectrum of neuropathologies, including tau-immunopositive neurofibrillary tangles and ubiquitin inclusions, might accompany nigral neuronal loss. These neuropathologies define the endpoint of many neurodegenerative disorders but might be symptomatic rather than causative. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) were recently discovered in late-onset parkinsonism, the phenotype of which can be clinically and pathologically indistinguishable from Parkinson's disease. However, in some kindreds with LRRK2- associated disease, pathologically distinct forms of parkinsonism, including nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary tangles, were discovered. Understanding the molecular function of the LRRK2 protein and its associated pathways might elucidate the switch between Lewy body pathology and neurofibrillary tangles, and holds promise for prospective therapeutics that might slow or halt progression of many forms of parkinsonism.

Animals↗
PubMed1993

Lack of the carboxyl terminal sequence of tau in ghost tangles of Alzheimer's disease.

Using seven independent antibodies against the amino terminal to the carboxyl terminal sequence of tau, we biochemically analyzed and compared the neuropathogenesis of two Alzheimer's disease brains from the viewpoint of abnormal processing on tau, the major constituent of paired helical filaments. One showed typical Alzheimer's disease with senile plaques and intracellular neurofibrillary tangles. The other showed advanced Alzheimer's disease with senile plaques and virtually the sole of ghost tangles without intracellular neurofibrillary tangles. We confirmed the previous observation that the carboxyl thirds of tau are tightly associated with paired helical filaments isolated in the presence of SDS. We found that biochemically, ghost tangles were abnormally phosphorylated and lacked the final carboxyl terminal sequence as well as the amino half of tau, unlike intracellular tangles. From these biochemical results taken together with the current evidence for ubiquitin in ghost tangles, we concluded that ghost tangles were extensively processed and irreversibly transformed into highly insoluble extracellular deposits.

Alzheimer Disease↗
PubMed1994

Tau immunoreactivity and SDS solubility of two populations of paired helical filaments that differ in morphology.

To further understand the processes that lead to the formation of neurofibrillary tangles from paired helical filaments (PHF) in Alzheimer brains, we studied two morphologically distinct fractions of PHF separated on sucrose density gradient. In a fraction with mostly short and non-aggregated PHF, the majority of filaments could be solubilized in SDS. In a fraction containing primarily PHF aggregated into clusters or bundles, sometimes resembling neurofibrillary tangles, filaments were less soluble in SDS. Immunogold labelling with a panel of tau-immunoreactive antibodies demonstrated that N-terminal epitopes of tau were preserved in the short filaments, but were reduced or absent in aggregated filaments. In contrast, C-terminal epitopes were present in both fractions. Furthermore, the accessibility of the microtubule-binding domain to immunolabelling was markedly impaired in short and non-aggregated filaments compared to aggregated filaments. These results are consistent with proteolytic degradation of the N-terminal epitopes and preservation of the C-terminal epitopes and the microtubule-binding domain of tau in the aggregated filaments. Partial proteolysis may be involved in the generation of aggregated PHF in neurofibrillary tangles.

Aged↗
PubMed1996

Apolipoprotein E in Guamanian amyotrophic lateral sclerosis/parkinsonism-dementia complex: genotype analysis and relationships to neuropathological changes.

Apolipoprotein E (Apo E) has been recently identified within amyloid deposits and neurofibrillary tangles in the brains of Alzheimer's disease (AD) patients. A strong association of the Apo E epsilon 4 allele with higher risk of developing AD has also been reported. In the present study, the distribution of Apo E and the possible relationship between Apo E alleles and neuropathological alterations were analyzed in a series of Guamanian amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) cases, a neurodegenerative condition characterized neuropathologically by widespread, severe neurofibrillary tangle formation but rare amyloid deposits. ApoE immunoreactivity was consistently observed in both type of lesions in these cases. Compared to tau protein immunoreactivity, there were generally fewer Apo E-immunoreactive neurofibrillary tangles, particularly in the deep layers of the neocortex and in the hippocampus. Genotype analysis revealed that the epsilon 4 allele frequency was 5.9%, the epsilon 3 allele frequency 88.2%, and the epsilon 2 allele frequency 5.9% in this series. Recent data suggest that the Apo E4 variant may induce amyloidogenesis, while E2 could have a neuroprotective role. However, the rare Guamanian patients with amyloid deposits in cortical areas were not related to the epsilon 4 allele, since all cases with senile plaques were epsilon 3/epsilon 3. In addition, compared to unaffected Guamanian cases and other Asian-Pacific populations previously reported, the observed low frequency of the epsilon 2 allele in the present cases, which may be consistent with the notion that this allele, may represent a neuroprotective factor in several neurodegenerative disorders. The present data indicate that there is a strong interaction between Apo E deposition and neurofibrillary changes in Guamanian ALS-PDC.

Aged↗
PubMed1993

Using the subcortically lesioned rat cortex to understand the physiological role of amyloid precursor protein.

Alzheimer's disease pathology is characterized by the presence of neuritic plaques and neurofibrillary tangles and specific neurotransmitter deficits in the cortex and hippocampus. Advances in the understanding of Alzheimer's disease have been hampered by the absence of appropriate animal model systems. Most in vivo rodent models have turned to aged animals, animals with experimentally induced lesions of various neurotransmitter systems, animals with pharmacologically induced neurotransmitter perturbations, and mice made transgenic for genes related to amyloid precursor protein. These models have been useful for the investigation of some discrete aspects of Alzheimer's disease, including deficits in forebrain cholinergic activity and the resulting cognitive deficits. However, none of these models have led to the development of the principal neuropathological hallmarks of Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Furthermore, the relationship, if any, between the reduction of neurotransmitter activity and the formation of neuritic plaques and neurofibrillary tangles is unknown. The subcortically lesioned rat model system which we have used approximates the cortical neurotransmitter and the cognitive deficits of Alzheimer's disease. We have recently found that these same subcortical neurotransmitter system lesions alter the expression of amyloid precursor protein, the precursor of beta amyloid peptide, which is the principal component of neuritic plaques. Loss of functional subcortical innervation by either permanent lesions or transient inhibition of cortical neurotransmitter (acetylcholine) release resulted in the induction of amyloid precursor protein in the cortex. The induction was rapid and persistent with the permanent lesions or reversible with the transient inhibition. Lesions cholinergic, serotonergic,and adrenergic neurotransmitter systems all resulted in the induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2003

Tau immunohistochemistry in acute brain injury.

Epidemiological studies have identified a history of head injury as a risk factor for Alzheimer's disease. However, the neuropathological mechanism underlying this relationship is as yet unclear. Neuronal cytoskeletal changes in the form of neurofibrillary tangles and neuropil threads have recently been demonstrated in young men who had sustained repetitive head injury and subsequently died in their 20s. In addition, recent experimental studies have found accumulation of tau within neuronal somata and damaged axons following diffuse brain injury. We hypothesized that tau-immunoreactive tangles may be present in the brains of patients who died after a single acute blunt head injury. A total of 45 cases of fatal head injury were immunostained for tau. They comprised nine groups (n=5 for each group) separated by age (0-19 years, 20-50 years, 50+ years) and survival time (<24 h, 24 h-1 week, 1 week-1 month) and were compared with age-matched controls. Subtle alterations in tau immunoreactivity, for example, in oligodendrocytes, were present in some head injury cases but not controls. However, neurofibrillary tangles did not appear more prevalent after traumatic brain injury (TBI) when compared with age-matched controls. Although alterations in tau immunoreactivity may occur which warrant further study, neurofibrillary tangles were not more prevalent after a single fatal episode of TBI.

Adolescent↗
PubMed1994

Neuropathologic changes of the temporal pole in Alzheimer's disease and Pick's disease.

OBJECTIVE: To describe the pattern of neuropathologic changes in temporal polar cortex in Alzheimer's disease (AD) in comparison with changes in Pick's disease (PD) and normal elderly cytoarchitecture. DESIGN: Examination of degenerative changes, neurofibrillary tangles, and senile plaques in the temporal poles of 10 patients with AD, three patients with PD, and five age-compatible control subjects, by means of thionein and thioflavine S stains and Alz-50 and ubiquitin immunocytochemistry. SUBJECTS: All patients had a documented history of dementia and AD or PD confirmed on neuropathologic examination. Control subjects were without a history of cognitive impairment or evident neuropathologic changes. OUTCOME MEASURES: Cytoarchitecture, neuronal loss, neurofibrillary tangles, senile plaques, and Pick bodies. RESULTS: All patients with AD showed atrophy of the temporal pole and marked neuronal loss, especially in layers III and V and, to a lesser degree, in layers II and VI. Heavy accumulation of neurofibrillary tangles was found in layers II, III, V, and VI. Patients with PD showed extensive neuron loss throughout, although this appeared to be most prominent in layer III. CONCLUSIONS: Both AD and PD pathologic changes severely affect the layers of the temporal pole that mediate widespread reciprocal connections with temporal and frontal cortices and limbic cortical and subcortical structures. Neural systems that interconnect temporal polar cortex with sensory association areas and memory-related limbic structures are, therefore, disrupted, and it is likely that these lesions play a role in the multifaceted cognitive and behavioral changes of AD and PD.

Adult↗
PubMed2005

Tau, tangles, and Alzheimer's disease.

Neurofibrillary tangles (NFT) are comprised of the microtubule-associated protein tau, in the form of filamentous aggregates. In addition to the well-known changes in phosphorylation state, tau undergoes multiple truncations and shifts in conformation as it transforms from an unfolded monomer to the structured polymer characteristic of NFT. Truncations at both the amino- and carboxy-termini directly influence the conformation into which the molecule folds, and hence the ability of tau to polymerize into fibrils. Certain of these truncations may be due to cleavage by caspases as part of the apoptotic cascade. In this review, we discuss evidence that strongly suggests that these truncations occur in an orderly pattern and directly influence the ability of tau to polymerize into filaments.

Alzheimer Disease↗
PubMed2006

It may take inflammation, phosphorylation and ubiquitination to 'tangle' in Alzheimer's disease.

Neurofibrillary tangles (NFT) are one of the pathologic hallmarks of Alzheimer's disease (AD). Their major component is tau, a protein that becomes hyperphosphorylated and accumulates into insoluble paired helical filaments. During the course of the disease such filaments aggregate into bulky NFT that get ubiquitinated. What triggers their formation is not known, but neuroinflammation could play a role. Neuroinflammation is an active process detectable in the earliest stages of AD. The neuronal toxicity associated with inflammation makes it a potential risk factor in the pathogenesis of chronic neurodegenerative diseases, such as AD. Determining the sequence of events that lead to this devastating disease has become one of the most important goals for AD prevention and treatment. In this review we focus on three topics relevant to AD pathology and to NFT formation: (1) what triggers CNS inflammation resulting in glia activation and neuronal toxicity; (2) how products of inflammation might change the substrate specificity of kinases/phosphatases leading to tau phosphorylation at pathological sites; (3) the relationship between the ubiquitin/proteasome pathway and tau ubiquitination and accumulation in NFT. The overall aim of this review is to provide a challenging and sometimes provocative survey of important contributions supporting the view that CNS inflammation might be a critical contributor to AD pathology. Neuronal cell death resulting from neuroinflammatory processes may have devastating effects as, in the vast majority of cases, neurons lost to disease cannot be replaced. In order to design therapies that will prevent endangered neurons from dying, it is critical that we learn more about the effects of neuroinflammation and its products.

Alzheimer Disease↗
PubMed1993

Neurofilament monoclonal antibodies RT97 and 8D8 recognize different modified epitopes in paired helical filament-tau in Alzheimer's disease.

Neurofibrillary tangles in Alzheimer's disease have been previously found to be labeled by some neurofilament antibodies that also recognize tau proteins. We have studied the reactivity of two such monoclonal antibodies, RT97 and 8D8, and of an anti-ubiquitin serum with the abnormal paired helical filaments (PHF)-tau (A68) polypeptides known to be the main component of the PHFs constituting the neurofibrillary tangles. 8D8 recognized the three major PHF-tau polypeptides, but RT97 reacted only with the two larger PHF-tau species. PHF-tau polypeptides were labeled by 8D8 and RT97 much more strongly than normal human tau and this labeling was decreased after alkaline phosphatase treatment. Anti-ubiquitin and anti-phosphotyrosine antibodies did not label PHF-tau polypeptides. The immunoreactivity of proteolytic fragments of PHF-tau polypeptides was studied with RT97, 8D8, and a panel of tau antibodies. The epitope for 8D8 on PHF-tau was localized between amino acids 222 and 427 in the carboxyl half of tau. The RT97 epitope on PHF-tau was localized in the amino domain of tau, probably in the 29-amino-acid insertion (insert 1) found towards the amino terminus of some tau isoforms. These results show that the basis for the labeling of neurofibrillary tangles by antibodies 8D8 and RT97 to neurofilament is their ability to react with PHF-tau polypeptides by recognizing sites specifically modified on PHF-tau, including a site specific to some tau isoforms.

Aged↗
PubMed1994

[Tau, amyloid and Alzheimer's disease].

Alzheimer's disease is a degenerative disorder of the human central nervous system that results in a progressive loss of memory and intellectual abilities. It is strongly related to aging and it is thus assumed that 0.5% of the total population, and up to 30% of eighty-year-olds suffer from the disease. Many require expensive institutional care, often over long periods, as there is no effective treatment at present. Abundant amyloid plaques and neurofibrillary tangles constitute the two major neuropathological lesions that characterize the brains of patients with Alzheimer's disease. The amyloid plaque consists mainly of a soluble polypeptide of 42-43 amino acids called beta-amyloid. beta-Amyloids is derived by an alternative cleavage of the much larger amyloid precursor protein (APP), but it is not known which proteolytic enzyme is responsible for this alternative cleavage. In contrast to plaques, the neurofibrillary tangles are formed intracellularly and the number of them seems to correlate with the progression of the disease. Their main components are paired helical filaments (PHF) which seem to consist almost entirely of the protein tau. The normal function of tau is to bind to microtubules and thereby stabilize the nerve cell's structure and integrity. In contrast to normal tau, PHF-tau is heavily phosphorylated, and it is assumed that this phosphorylation is the underlying cause of the formation of PHF and the neurofibrillary tangles. Despite extensive research it is still not known which enzymes are responsible for the over phosphorylation of tau that occurs in Alzheimer's disease. If they could be identified and controlled pharmacologically, an effective treatment of the disease might be possible.

Alzheimer Disease↗
PubMed2001

Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome.

CONTEXT: Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes. OBJECTIVE: To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome. METHODS: Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital. RESULTS: The principal observations included the presence of intraneuronal Abeta immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Abeta) and the formation of senile plaques and neurofibrillary tangles. CONCLUSIONS: We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Abeta in neurons and astrocytes, (2) deposition of extracellular Abeta and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.

Adolescent↗
PubMed2005

Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center.

BACKGROUND: Epidemiologic studies have implicated cerebrovascular disease and its antecedents as risk factors for Alzheimer disease (AD). Cerebral atherosclerosis or strokes may increase the deposition of neuritic plaques or the formation of neurofibrillary tangles. Alternatively, they may simply hasten the age at onset of disease, or increase the severity of disease symptoms. This investigation examined the association between cerebrovascular disease and the pathologic manifestations of AD in an autopsy series. METHODS: This was a cross-sectional study using data from the United States National Alzheimer's Coordinating Center database. The primary analysis included 1,054 individuals with clinical information and semiquantitative neuropathologic measurements: 921 had AD as the primary neuropathologic diagnosis and 133 were considered neuropathologically normal. RESULTS: Overall, 9% of the individuals had clinical history of stroke during life, but 33% had evidence of cerebral infarcts at postmortem. There was no association between neuritic plaques or neurofibrillary tangles, the primary neuropathologic manifestations of AD, with either clinical history of stroke or the presence of cerebral infarcts at postmortem. The authors did find a higher frequency of neuritic plaques and neurofibrillary tangles with increased amyloid angiopathy. Neither plaques nor tangles were associated with small vessel cerebrovascular disease, arteriosclerosis. However, the presence of large-vessel cerebrovascular disease, or atherosclerosis, was strongly associated with an increased frequency of neuritic plaques. CONCLUSIONS: Atherosclerotic cerebrovascular disease may have a role in the pathogenesis of Alzheimer disease, because of a strong association with frequent neuritic plaques.

Age of Onset↗
PubMed1990

Hippocampal formation: anatomy and the patterns of pathology in Alzheimer's disease.

Anatomical studies of the primate brain have shown that the subicular and CA1 allocortices give rise to hippocampal efferents that course to numerous telencephalic and diencephalic targets including other parts of the cortex. The hippocampal formation is damaged heavily in Alzheimer's disease, and is a focal point for pathology. We examined the anteroposterior extent of the hippocampal formation in 52 cases of Alzheimer's disease, 6 cases of other types of dementia and 10 age-compatible controls, to determine the patterns of pathology. We have observed that only certain subfields of the hippocampal formation are affected by cell loss, neurofibrillary tangles and neuritic plaques, while adjacent, anatomically distinct subfields are relatively spared. The portions of the hippocampal formation most crucial for both cortical and subcortical efferent projections are severely affected by Alzheimer pathological changes. Most notable are neurofibrillary tangles in the subicular and CA1 subfields. Layer IV of entorhinal cortex, specifically affected by neurofibrillary tangles. Hippocampal input is also compromised. For example, layer II of entorhinal cortex, which gives rise to perforant pathway hippocampal afferents, also undergoes severe neurofibrillary changes. Neuritic plaques appear in a distinct layer in the terminal zone of the perforant pathway, which carries the majority of corticohippocampal afferents. Plaques are also common in a zone that receives serotoninergic projections from the raphe complex, thus compromising another hippocampal afferent. In sum, these changes disrupt intrinsic and extrinsic hippocampal circuitry at multiple levels, and the pathological dissection deprives the hippocampal formation of many of its efferent and afferent connections with cortical and subcortical structures important in memory-related neural systems. These changes likely contribute to the memory impairment that characterizes Alzheimer's disease and the devastating intellectual decline that ensues.

Aged↗
PubMed1992

Alzheimer's disease: is the decrease of the cholinergic innervation of the hippocampus related to intrinsic hippocampal pathology?

Consistent findings in the hippocampi of patients with Alzheimer's disease are the presence of neurofibrillary tangles in pyramidal neurons and the loss of choline acetyltransferase activity due to degeneration of hippocampal cholinergic terminals. The present study sought to clarify, in the brains of five patients with Alzheimer's disease and four controls, whether the loss of cholinergic terminals in the hippocampal stratum pyramidale in Alzheimer's disease is related to degenerative changes in hippocampal pyramidal cells. A polyclonal antibody to human choline acetyltransferase was employed to visualize immunohistochemically cholinergic terminals. Hippocampal neurons were stained with Cresyl Violet, neurofibrillary tangles with thioflavin S and a monoclonal antibody against phosphorylated neurofilament (RT97). Quantification of the stained structures was performed in CA4, CA1 and the subiculum, on five sections selected from the entire anteroposterior extent of each hippocampus. In the group of Alzheimer patients, the densities of cholinergic terminals were homogeneously diminished in the three hippocampal subregions in comparison with the controls (32-33%). In contrast, a significant loss of pyramidal neurons was found only in CA1, and the density of neurofibrillary tangles was markedly increased only in CA1 and the subiculum in Alzheimer's disease. These findings suggest that there is no relationship between the loss of cholinergic terminals and the degeneration of pyramidal cells in the hippocampus of patients with Alzheimer's disease.

Aged↗