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T Arendt

Publications and source records attributed to T Arendt.

At least 145 records · Page 8Linked to original sources
PubMed1987

The cholinergic system in aging.

A morphometric analysis of neuronal loss during normal aging was performed in the nucleus basalis Meynert complex of the basal forebrain (Nbm) (nucleus septi medialis, nucleus of Broca's diagonal band, nucleus basalis) and the ciliary ganglion, a peripheral cholinergic structure, in patients free of neurological and psychiatric illness. As a basis for morphometric evaluation of the Nbm complex, a three-dimensional reconstruction of this complex structure was made. Neuronal counts in the Nbm complex and the ciliary ganglion remained stable up to the age of 60 or 50 years, respectively. After this age the number of neurons declined moderately in ciliary ganglion in all cases studied as well as in the Nbm complex in some cases (-20 and -25%, respectively, at about 90 years of age). In 3 out of 8 cases older than 60 years, neuronal counts in the Nbm complex were not reduced, so that no significant decline in neuronal number is apparent from the mean values of the 17 cases studied. No age-related changes were found in the neuronal distribution amongst the different subgroups of Nbm neurons using the alternative nomenclature of Mesulam et al. [J. comp. Neurol. 214: 170-197, 1983]. Our results provide no evidence that the cortical cholinergic projection system and peripheral cholinergic neurons might be especially vulnerable during normal aging. The severe degeneration of the cholinergic cortical projection system in SDAT is probably caused by mechanisms different from those acting during normal aging.

Adult↗
PubMed1986

Dendritic changes in the basal nucleus of Meynert and in the diagonal band nucleus in Alzheimer's disease--a quantitative Golgi investigation.

Golgi-impregnated reticular neurons and multipolar giant neurons, the two main classes of neurons in the basal nucleus of Meynert and in the diagonal band nucleus, were investigated morphometrically in five cases of Alzheimer's disease, and compared to controls. Both degenerative as well as regenerative neuronal changes were observed in cases of Alzheimer's disease. Degenerative changes such as irregular swellings and the fragmentation of dendrites are most pronounced on reticular neurons but can also be detected to a lesser extent on multipolar giant neurons. Regenerative changes are restricted to reticular neurons. They are characterized by the appearance of perisomatic filopodia, by an increase in the size of cell soma, by an increase in the degree of dendritic arborization and spatial extension of the dendritic tree. These regenerative changes are probably signs of a compensatory mechanism which might be induced by degeneration in this area.

Alzheimer Disease↗
PubMed1985

Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease.

In order to substantiate the hypothesis of a cholinergic pathogenesis of neuritic plaques in Alzheimer's disease the relationship between the loss of cholinergic neurons in six subdivisions of the nucleus basalis of Meynert and density of neuritic plaques in five neocortical target areas and hippocampus was studied in five cases with Alzheimer's disease. Distribution of plaques in different cortical areas as well as degeneration pattern of neurons within the subpopulations of the nucleus basalis were markedly different in the cases of Alzheimer's disease. Quantitative evaluation of the number of neuritic plaques in the five cortical areas revealed a strong correlation with the loss of neurons in those subpopulations of the nucleus basalis which give rise to the cholinergic innervation of the affected cortical areas. The nonlinearity of this correlation may reflect two different modes of plaque formation. Either plaque formation is a self-perpetuating process with an increasing rate depending on the number of plaques already formed or additional mechanisms, with an increasing rate of influence during plaque formation are induced. The shape of the regression function is different for the various cortical regions and their corresponding subpopulations of the nucleus basalis suggesting a different dependency of neuritic plaque formation on the neuronal loss in the nucleus basalis. This might reflect a different density of cholinergic fibers within these areas, a different degree of collateralization of the fibers or other factors not yet known. The findings indicate that degeneration of cortical cholinergic afferents from the neurons of the nucleus basalis is an important feature in the pathogenesis of neuritic plaques.

Aged↗
PubMed1984

Correlation between cortical plaque count and neuronal loss in the nucleus basalis in Alzheimer's disease.

In order to substantiate the hypothesis of a cholinergic matrix for neuritic plaque formation in Alzheimer's disease (AD), the relationship between the loss of cholinergic neurons in the basal forebrain and formation of neuritic plaques in the cerebral cortex was studied in 5 cases of neuropathologically verified AD. Quantitative evaluation of the number of neuritic plaques in the cerebral cortex as calculated from 6 areas showed a strong correlation with the loss of neurons in the nucleus basalis of Meynert (NbM). This finding indicates that changes in cortical cholinergic innervation which arise from the neurons of the NbM are an important feature in the pathogenesis of neuritic plaques.

Acetylcholinesterase↗
PubMed1984

Neurone loss in the nucleus basalis of Meynert in Creutzfeldt-Jakob disease.

In a man of 47 with a 2-month history of Creutzfeldt-Jakob-disease verified neuropathologically a morphometric study of the nucleus basalis of Meynert, the major source of cholinergic innervation of the cortex, revealed a neuronal loss of 45%. The degeneration of these neurones may provide the morphological substrate of the cortical cholinergic deficiency which has been reported in this condition. The six subpopulations of the nucleus basalis were affected in different degrees. Neuronal loss was most pronounced in those subpopulations which project to cortical areas most affected by spongiosis and neuronal loss. It is suggested that maintenance of the nucleus basalis complex is a necessary condition for higher cortical function.

Basal Ganglia↗
PubMed1983

Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease.

The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compared to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.

Alcohol Amnestic Disorder↗
PubMedDate not supplied

Effects of bile salt exposure on pancreatic duct barrier function and protein release determined by two-dimensional electrophoresis and lectin-affinoblotting.

We analyzed effects of a bile salt on pancreatic duct barrier function and protein release into pancreatic juice in cats, using two-dimensional-electrophoresis and lectin-affinoblotting. Preanalyzed pancreatic juice was perfused along the pancreatic duct following duct exposure to a bile salt. In this case, pancreatic duct mucosa showed a partial loss of barrier function to the leakage of exocrine pancreatic proteins dependent upon molecular weight and charge. The release of a sialic acid possessing protein into pancreatic juice was observed.

Acute Disease↗
PubMedDate not supplied

Alzheimer's disease as a presumptive threshold phenomenon.

With the example of the basal forebrain cholinergic system as a site of primary importance in AD, the existence of a critical neuron loss as a threshold between normal aging and AD is suggested. If the extent of degeneration exceeds this threshold the system decompensates and the clinical picture becomes apparent. The fully developed stage of AD might, therefore, represent a condition beyond the capacity of compensation where plastic adaptive changes are still present but functionally insufficient.

Acetylcholine↗
PubMedDate not supplied

Hyperphosphorylated protein tau is restricted to neurons devoid of perineuronal nets in the cortex of aged bison.

Hyperphosphorylated tau in the cortex and hippocampal formation of two aged bisons was characterized by its immunoreactivity to the phospho-epitope-recognizing monoclonal antibodies AT8, AT100, PHF-1 and TG-3. Gallyas silver staining revealed sparsely scattered cortical tangles and neuropil threads. In dual-peroxidase staining experiments, the immunocytochemical detection of vulnerable neurons was combined with the demonstration of chondroitin sulphate proteoglycan-rich perineuronal nets of the extracellular matrix. Such polyanionic lattice-like neuronal coatings were revealed lectin- and immunocytochemically. Hyperphosphorylated tau was exclusively observed in neurons devoid of perineuronal nets. The present findings in the aged bison parallel previously obtained results from a quantitative study of human brains affected by Alzheimer's disease. In conclusion, the low susceptibility of different types of neurons to the abnormal phosphorylation of tau corresponds to high proportions of certain chondroitin sulphate proteoglycans in their microenvironment.

Age Factors↗
PubMedDate not supplied

Alzheimer's disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain.

Degeneration in AD primarily occurs in a subset of neurons that in the adult brain retain a high degree of structural plasticity and in these neurons is associated with the activation of mitogenic pathways and a cell cycle re-entry. Brain areas affected by AD pathology are those structures involved in the regulation of "higher brain functions" that become increasingly predominant as the evolutionary process of encephalization progresses, such as hippocampus, neocortical association areas and the cholinergic basal forebrain neurons. The functions these areas subserve such as learning, memory, perception, self-awareness, and consciousness require a life-long re-fitting of synaptic contacts that allows for the acquisition of new epigenetic information. This adaptive reorganization of neuronal connectivity in the mature brain is based upon the strengthening of existing synapses, the formation of new synapses and the destabilization of previously established synaptic contacts. With the increasing need during evolution to organize brain structures of increasing complexity, these processes of dynamic stabilization and de-stabilization become more and more important but might also provide the basis for an increasing rate of failure. A hypothesis is proposed that it is the 'labile state of differentiation' (G0-arrest) of a subset of neurons in the adult brain that allows for ongoing morphoregulatory processes after development is completed but at the same time renders these neurons particularly vulnerable. The delicate balance between G0-arrest and G1-entry might be prone to a variety of potential disturbances during the lifetime of an individual. Morphodysregulation in AD, accompanied by an activation of intracellular mitogenic signaling might, thus, be a slowly progressing dysfunction that eventually overrides the differentiation control and results in dedifferentiation, a condition in conflict with the otherwise 'mature' background of the nervous system. Cell-cycle and differentiation control might thus provide the link between structural brain self-organization and neurodegeneration that both are unique to human.

Adult↗
PubMedDate not supplied

Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly.

The sensitivity of MRI volumetric measures to detect cognitive dysfunction is examined in 39 participants of an epidemiological field study (age 75-85, MMSE 19-30). According to Clinical dementia rating (CDR), 17 subjects had normal cognition (CDR 0), 12 had questionable (CDR 0.5) and 10 mild dementia (CDR 1). Discriminant analysis based on four hippocampal measures resulted in a correct classification of 76.9% of all subjects. Left-sided and posterior hippocampal measures were more responsible for group discrimination than right-sided and anterior measures. In CDR 0.5, a significant hippocampal volume reduction of 14.3% vs.11.3% (left vs. right) relative to normal was found. The right hippocampus was significantly greater than the left in CDR 0 and CDR 0.5, but not in CDR 1. The magnitude of non-directional hippocampal asymmetry increased with decreasing cognitive state. We conclude that hippocampal atrophy is sensitive to detect cognitive dysfunction and subjects at risk for Alzheimer's disease in the elderly population.

Aged↗
PubMedDate not supplied

Phosphorylation of tau, Abeta-formation, and apoptosis after in vivo inhibition of PP-1 and PP-2A.

Chronic inhibition of protein phosphatases 1 and 2A in vivo was induced by infusion of okadaic acid into lateral ventricles of rat brain for up to 4 months. Cytoskeletal pathology, alterations of the amyloid precursor protein, and apoptotic cell death induced by this treatment followed a certain sequence and spatial distribution. Changes in the expression, phosphorylation, and subcellular distribution of neurofilament proteins and tau, as well as first signs of apoptotic cell death, occurred already after about 2 weeks. The distribution of apoptotic cells, however, was different from those revealing a high accumulation of hyperphosphorylated tau, indicating that those cytoskeletal pathology had no obvious sequelae for the viability of these neurones. A continuation of treatment for longer than 2 weeks induced diffuse deposits of both hyperphosphorylated tau and A beta-amyloid-immunoreactive material in white matter areas that increased in size and number over time. Because tau-phosphorylation is a regulator of the dynamic stability of microtubules, the pathology observed in the present experimental paradigm in the white matter might be viewed as an indication of a disturbed axonal transport. It is hypothesized that perturbations of the axonal transport might also be critically involved in the formation of paired helical filaments and amyloid deposits in Alzheimer's disease.

Amyloid beta-Peptides↗
PubMedDate not supplied

Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology.

In terminal Alzheimer's disease (AD) the frequency of plaques was found to be reduced in single cases. To test this finding in a larger sample, and in order to determine whether the number of plaques labeled with different markers and the distribution of neurofibrillary tangles are correlated positively to each other and to the degree of dementia, a sample of 134 autopsy brains with and 15 without AD-related pathology has been examined. All of the cases were staged according to Braak and Braak. Both the frequency of plaques immunopositive for beta-amyloid, amyloid precursor protein, and apolipoprotein E and that of microglial cells in the cortex and in the white matter were determined semiquantitatively. The content and distribution of PHF-tau was ascertained by ELISA and immunohistochemistry. Both the clinical dementia rating and the global deterioration scale were used as clinical parameters retrospectively. Correlation coefficients were calculated for all parameters and differences were evaluated statistically. With progressive distribution of neurofibrillary tangles and increasing content of PHF-tau the plaque stages and the degree of cortical microglia reaction increased up to the Braak-stages IV and V, thereafter showing a slightly decreasing tendency in the investigated regions. In end-stage AD resorption of beta-amyloid seems to surpass its deposition. The microglial reaction in the white matter correlated neither with the Braak-stage nor with the accumulation of amyloid. With regard to the degree of dementia, both scales correlated well with the pathological changes. Our data show that neuronal cytoskeletal alterations progressively increase with progressive dementia until the end stage of AD in contrast to the frequencies of plaques and cortical microglial cells, and are therefore preferable for staging purposes.

Aged↗
PubMedDate not supplied

Postmortem changes in the phosphorylation state of tau-protein in the rat brain.

The phosphorylation state of tau-protein is crucial for the regulation of neuronal microtubule organization. Functional conclusions on tau-protein require an accurate assessment of phosphorylated sites. Therefore, the in vivo distribution and postmortem preservation of some phospho-epitopes on tau-protein were examined in the rat brain under different fixation and preparation conditions. Detection of tau-protein with a phosphorylation-independent antiserum revealed both axonal and somatodendritic localizations, which were not influenced by a postmortem interval of 30 min. The phospho-epitopes recognized by 12E8, AT8, and PHF-1 were mainly localized in the somatodendritic compartment. The binding sites of AT8 and PHF-1 were rapidly dephosphorylated postmortem, whereas the Tau-1 epitope was unmasked in the somatodendritic region. The axonally located phospho-epitope of AT270 and the nuclear epitope of AT100 were still detectable after a postmortem interval of 30 min. Postmortem dephosphorylation and inhibition of this process by PP1 and/or PP2A was further demonstrated on Western blot. In conclusion, rapid processing of tau-protein is essential for the correct assessment of investigations on phospho-isoforms.

Animals↗
PubMedDate not supplied

Muscarinic acetylcholine receptors activate the acetylcholinesterase gene promoter.

The acetylcholinesterase (AChE) gene promoter contains several overlapping binding sites for Sp1 and Egr-1 transcription factors. Cotransfection experiments and promoter assays showed that Egr-1 can potently activate transcription from the human AChE promoter. Muscarinic acetylcholine receptors (mAChR) rapidly activate, via protein kinase C-mediated signaling, expression of the Egr-1 gene, leading to dramatically increased nuclear concentrations of Egr-1 protein, and to increased binding of Egr-1 to specific DNA recognition sequences. These mAChR-induced increases are followed by increased transcription from the human AChE promoter. In vivo studies with intraventricular infusions of the cholinergic immunotoxin 192 IgG saporin showed more than 80% decrease of AChE activity in cholinergic target areas of the hippocampus and brain cortex. The results are compatible with a combination of decreased AChE activity in degenerating subcortical cholinergic projections, and additional decreases in postsynaptic AChE gene expression. Together our data show that mAChR can activate transcription from the AChE promoter via increased synthesis of Egr-1. The results suggest a feedback mechanism by which the AChE gene is activated by cholinergic neurotransmission, possibly leading to increased formation of AChE protein and accelerated degradation of acetylcholine at cholinergic synapses. This possibility suggests testing of cholinomimetic compounds currently in development for the treatment of Alzheimer's disease for their potential ability to increase AChE gene expression.

Acetylcholinesterase↗