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At least 595 records · Page 33Linked to original sources
PubMed1994

Formation of amyloid-like substance from beta-2-microglobulin in vitro. Role of serum amyloid P component: a preliminary study.

Although the pathogenesis has yet to be fully understood, beta 2-microglobulin (beta 2m) related amyloidosis is a frequent complication in long-term hemodialysis (HD) patients. In an attempt to clarify the association of two potential candidates with amyloidogenesis from beta 2m in HD patients, human urine-derived beta 2m solution alone or combined with glycosaminoglycans: hyaluronic acid, heparan sulfate, or serum amyloid P component (SAP) were dialyzed against physiological buffered solution (pH 7.4) using a microdialyzer in vitro for 72 h at 4 degrees C. This study demonstrates for the first time that SAP can play a crucial role in the formation of amyloid-like fibrils from beta 2m. This occurs by a direct influence on either the processing of a precursor protein, or protein folding, in vitro, by a short-period dialysis against a physiological buffered solution.

Amyloid↗
PubMed2005

Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats.

BACKGROUND AND PURPOSE: The present study examined the long-term presence of beta-amyloid precursor protein (APP) and beta-amyloid (Abeta) accumulation in the rat thalamus after focal cerebral ischemia. METHODS: Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 hours. Sensorimotor outcome was assessed using a tapered/ledged beam-walking task after operation. The distribution of APP and Abeta was examined immunohistochemically at 1 week, 1 month, and 9 months after MCAO. RESULTS: MCAO caused a long-lasting deficit in forelimb and hind limb function assessed using the beam-walking test. Histologic examination revealed a transient increase in APP and Abeta staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and Abeta deposits persisted in the thalamic nuclei (ventroposterior lateral and ventroposterior medial nuclei), eventually leading to dense plaque-like deposits by the end of the 9-month follow-up. The deposits were surrounded by an astroglial scar. The deposits were positive for Abeta and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of Abeta, ie, Abeta42 and Abeta40, showed a preferential staining for Abeta42. Congo red or thioflavine S did not stain the deposits. CONCLUSIONS: The present results demonstrated the persistent presence and aggregation of APP and Abeta, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia.

Amyloid beta-Peptides↗
PubMed1998

beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion: effect of age.

BACKGROUND AND PURPOSE: Previous studies have shown that the ss-amyloid precursor protein (ssAPP) is upregulated after cerebral ischemia and that the ss-amyloid (Ass) fragment may be toxic to brain cells. Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. To test the hypothesis that the upregulation and/or persistence of amyloidogenic proteins is exacerbated in aged rats after cerebral ischemic stroke, we studied the expression of ssAPP and its proteolytic product Ass in the brains of young and old rats 7 days after temporary cerebral ischemia. METHODS: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. After 1 week, brains were removed and immunostaining was performed for ssAPP, Ass, and ED1 for macrophages and glial fibrillary acidic protein (GFAP). RESULTS: Histological staining revealed that the degree of necrotic cavitation in the infarct core was relatively less in aged rats than in young rats, suggesting a slower pace of degenerative change and/or tissue removal in older animals. ssAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1-positive cells in the infarct core and in the penumbra of both young and aged animals. Ass immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Ass-immunoreactive minispheres were more numerous in aged rats than in young rats. CONCLUSIONS: The presence of ssAPP and Ass immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of ssAPP and its proteolytic fragments, especially in the aged brain.

Aging↗
PubMed2004

Decreased levels of soluble amyloid beta-protein precursor and beta-amyloid protein in cerebrospinal fluid of patients with systemic lupus erythematosus.

Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). These symptoms are extremely diverse, including a state of dementia. The aim of this study was to examine the cerebrospinal fluid (CSF) content of soluble molecules indicating axonal degeneration and amyloidogenesis. One hundred and fourteen patients with SLE and age-matched controls were evaluated clinically, with magnetic resonance imaging of the brain and CSF analyses. Levels of tau, amyloid precursor protein (APP), beta-amyloid protein (Abeta42), and transforming growth factor beta (TGF-beta) were all determined using sandwich ELISAs.APP and Abeta42 levels were significantly decreased in SLE patients irrespective of their CNS involvement, as compared with healthy controls. Patients with neuropsychiatric SLE who underwent a second lumbar puncture following successful cyclophosphamide treatment showed further decreases of Abeta42. CSF-tau levels were significantly increased in SLE patients showing magnetic resonance imaging-verified brain pathology as compared with SLE patients without such engagement. Importantly, tau levels displayed significant correlation to Abeta42 levels in the CSF. Finally, TGF-beta levels were significantly increased in patients with neuropsychiatric SLE as compared with those without. Low intrathecal levels of Abeta42 found in SLE patients seem to be a direct consequence of a diminished production of APP, probably mediated by heavy anti-inflammatory/immuno-suppressive therapy. Furthermore, our findings suggest that CSF tau can be used as a biochemical marker for neuronal degeneration in SLE. Finally, the increased TGF-beta levels observed may support a notion of an ongoing anti-inflammatory response counteracting tissue injury caused by CNS lupus.

Adolescent↗
PubMed2005

The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain.

The fetal basis of adult disease (FeBAD) hypothesis states that many adult diseases have a fetal origin. According to FeBAD, injury or environmental influences occurring at critical periods of organ development could result in "programmatic" changes via alterations in gene expression or gene imprinting that may result in functional deficits that become apparent later in life. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by excessive deposits of aggregated beta-amyloid (Abeta) peptides, which are snippets of the beta-amyloid precursor protein (APP). The predominantly sporadic nature of AD suggests that the environment must play a role in neurodegeneration. To examine latent responses to an environmental agent, we exposed rodents to lead and monitored the lifetime expression of the APP gene. We observed that APP mRNA expression was transiently induced in neonates, but exhibited a delayed overexpression 20 months after exposure to Pb had ceased. This upregulation in APP mRNA expression was commensurate with a rise in activity of the transcription factor Sp1, one of the regulators of the APP gene. Furthermore, the increase in APP gene expression in old age was accompanied by an elevation in APP and its amyloidogenic Abeta product. In contrast, APP expression, Sp1 activity, as well as APP and Abeta protein levels were unresponsive to Pb exposure during old age. These data suggested that environmental influences occurring during brain development predetermined the expression and regulation of APP later in life, potentially altering the course of amyloidogenesis.

Aging↗
PubMed2006

The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological changes, including the deposition of amyloid beta (Abeta) in senile plaques. The mechanisms causing the disease and Abeta accumulation are not well understood, but important genetic associations with apolipoprotein E genotype and involvement of lipoprotein receptors have become apparent. LR11 (also known as SorLA), a member of the low-density lipoprotein receptor family, has been identified previously as an altered transcript in microarray analyses of samples from human AD cases. Here, we show neuronal expression of the lipoprotein receptor LR11 in control brain in regions vulnerable to AD neuropathology and marked reduction of LR11 expression in these regions in AD brains before cell death. Overexpression of LR11 drastically reduces levels of extracellular Abeta and also lowers levels of total cellular amyloid precursor protein (APP). LR11 colocalizes with APP and regulates its trafficking in endocytic compartments, which are important intracellular sites for APP processing and Abeta generation. Endogenous LR11 localizes to neuronal multivesicular bodies in both rat and human brain. The robust correlation between reduced LR11 expression and AD neuropathology and its potent effects on extracellular Abeta levels suggest that this neuronal lipoprotein receptor could play an important role in AD pathogenesis.

Alzheimer Disease↗
PubMed2002

Implications of amyloid precursor protein and subsequent beta-amyloid production to the pharmacotherapy of Alzheimer's disease.

Alzheimer's disease is the most common type of dementia in older people. It is highly prevalent, affecting 35-45% of those aged 85 years or older. This disease has devastating consequences to patients, their families, caregivers, and the health care system. Much has been learned about its pathobiology, which has led to the beta-amyloid (Abeta) hypothesis. This hypothesis continues to be the predominant postulate of the pathobiology of Alzheimer's disease. Under this hypothesis, abnormal accumulation of Abeta is followed by a cascade of neurotoxic effects, which eventually result in neurodegeneration and development of Alzheimer's disease. This is thought to be the result of altered processing of the amyloid precursor protein (APP), preferentially by beta- and gamma-secretase enzymes rather than nonamyloidogenic processing by alpha-secretase. The growing body of knowledge regarding the processing of APP to various forms of Abeta has resulted in new approaches to the investigation of putative anti-Alzheimer's disease compounds, including immune-based therapies and various agents that can positively affect APP processing.

Alzheimer Disease↗
PubMed2002

Amyloid beta antagonizes insulin promoted secretion of the amyloid beta protein precursor.

Amyloid beta (Abeta) peptides are direct competitive inhibitors of insulin binding and action [25]. We demonstrate that Abeta peptides can inhibit the effect of insulin on the metabolic processing of the amyloid beta protein precursor (AbetaPP). As evidence emerges concerning the role of insulin and insulin like growth factors (IGFs) in learning and memory, recent findings have suggested that insulin may have a significant role in the pathogenetic pathways leading to Alzheimer's disease (AD). As an example several investigators have demonstrated upregulation of insulin receptors and defective insulin receptor signal transduction in AD brains. Moreover insulin has been shown to positively modulate AbetaPP proteolytic processing. The fact that insulin and Abeta appear to share a common system for degradation and disposal as they are both substrates of the insulin degrading enzyme (IDE) suggested the possibility of a reciprocal interference. Here we report that Abeta can directly interfere with insulin receptor signalling inhibiting the autophosphorylation of partially purified insulin receptors. As a consequence of such interaction we also demonstrate that Abeta blocks the effect of insulin on the release of sAbetaPPalpha in chinese hamster ovaries (CHO) cells transfected with insulin receptors.

Alzheimer Disease↗
PubMed2002

Nicotine lowers the secretion of the Alzheimer's amyloid beta-protein precursor that contains amyloid beta-peptide in rat.

Reports of an inverse relationship between nicotine intake, due to cigarette smoking, and the incidence of Alzheimer's disease (AD) prompted us to investigate the effects of nicotine on amyloid beta-protein precursor (AbetaPP) processing in rat. Over-production and/or altered metabolism of AbetaPP, resulting in increased amyloid beta-peptide (Abeta), appear pivotal in the pathogenesis of AD. Abeta is generated proteolytically from betaPP by a group of secretases. AbetaPP cleavage by gamma-secretase results in the secretion of a truncated soluble betaPP (sAPPgamma) that contains intact Abeta. Nicotine, 1 and 8 mg/kg/day, doses commensurate with cigarette smoking and a higher but well tolerated dose, respectively, was administered over 14 days and Western blot analysis was performed on sAPP fragments. Both doses significantly reduced sAPPgamma. These actions were blocked by nicotinic receptor antagonism. Whereas nicotinic antagonists alone had no effect on either total sAPP or sAPPgammalevels in CSF, muscarinic antagonism significantly elevated them; suggesting that muscarinic rather than nicotinic receptor silence alters processing of AbetaPP to favor a potentially amyloidogenic route. Combined nicotine and muscarinic antagonism attenuated the action of the latter to elevate sAPPgamma, indicating that nicotine modifies AbetaPP processing away from potentially amyloidogenic products. These results suggest that within the brain, levels of total sAPP, sAPPgamma and, accordingly, Abeta are subject to cholinergic manipulation, offering therapeutic potential at the level of AbetaPP processing to decrease Abetadeposition.

Alzheimer Disease↗
PubMed2006

Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: a role in Alzheimer's disease?

Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and AbetaPP and Abeta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at > or = 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples.

Acetylcholine↗
PubMed1999

Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion.

Previous studies have demonstrated that amyloid precursor protein (APP) can bind and reduce Cu(II) to Cu(I), leading to oxidative modification of APP. In the present study we show that adding copper to Chinese-hamster ovary (CHO) cells greatly reduced the levels of amyloid Abeta peptide (Abeta) both in parental CHO-K1 and in copper-resistant CHO-CUR3 cells, which have lower intracellular copper levels. Copper also caused an increase in the secretion of the APP ectodomain, indicating that the large decrease in Abeta release was not due to a general inhibition in protein secretion. There was an increase in intracellular full-length APP levels which paralleled the decrease in Abeta generation, suggesting the existence of two distinct regulating mechanisms, one acting on Abeta production and the other on APP synthesis. Maximal inhibition of Abeta production and stimulation of APP secretion was achieved in CHO-K1 cells at about 10 microM copper and in CHO-CUR3 cells at about 50 microM copper. This dose 'window of opportunity' at which copper promoted the non-amyloidogenic pathway of APP was confirmed by an increase in the non-amyloidogenic p3 fragment produced by alpha-secretase cleavage. Our findings suggest that copper or copper agonists might be useful tools to discover novel targets for anti-Alzheimer drugs and may prove beneficial for the prevention of Alzheimer's disease.

Amino Acid Sequence↗
PubMed2000

Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques.

Insulysin (EC. 3.4.22.11) has been implicated in the clearance of beta amyloid peptides through hydrolytic cleavage. To further study the action of insulysin on Abeta peptides recombinant rat insulysin was used. Cleavage of both Abeta(1-40) and Abeta(1-42) by the recombinant enzyme was shown to initially occur at the His(13)-His(14), His(14)-Gln(15), and Phe(19)-Phe(20) bonds. This was followed by a slower cleavage at the Lys(28)-Gly(29), Val(18)-Phe(19), and Phe(20)-Ala(21) positions. None of the products appeared to be further metabolized by insulysin. Using a rat cortical cell system, the action of insulysin on Abeta(1-40) and Abeta(1-42) was shown to eliminate the neurotoxic effects of these peptides. Insulysin was further shown to prevent the deposition of Abeta(1-40) onto a synthetic amyloid. Taken together these results suggest that the use of insulysin to hydrolyze Abeta peptides represents an alternative gene therapeutic approach to the treatment of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed2001

Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling.

Alzheimer's Disease (AD) is characterized by cerebral accumulation of beta-amyloid peptides (Abeta), which are proteolytically derived from beta-amyloid precursor protein (betaAPP). betaAPP metabolism is highly regulated via various signal transduction systems, e.g., several serine/threonine kinases and phosphatases. Several growth factors known to act via receptor tyrosine kinases also have been demonstrated to regulate sbetaAPP secretion. Among these receptors, insulin and insulin-like growth factor-1 receptors are highly expressed in brain, especially in hippocampus and cortex. Emerging evidence indicates that insulin has important functions in brain regions involved in learning and memory. Here we present evidence that insulin significantly reduces intracellular accumulation of Abeta and that it does so by accelerating betaAPP/Abeta trafficking from the trans-Golgi network, a major cellular site for Abeta generation, to the plasma membrane. Furthermore, insulin increases the extracellular level of Abeta both by promoting its secretion and by inhibiting its degradation via insulin-degrading enzyme. The action of insulin on betaAPP metabolism is mediated via a receptor tyrosine kinase/mitogen-activated protein (MAP) kinase kinase pathway. The results suggest cell biological and signal transduction mechanisms by which insulin modulates betaAPP and Abeta trafficking in neuronal cultures.

Alzheimer Disease↗
PubMed2001

[From gene to disease; amyloid-beta precursor protein gene instrumental in hereditary cerebral amyloid angiopathies].

Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by a mutation in the amyloid precursor protein gene on chromosome 21. The disease is characterised by amyloid deposition in cerebral blood vessels, which results in cerebral haemorrhages, leucencephalopathy, dementia and death. In the same gene, mutations have also been found for other rare diseases which also result in dementia and haemorrhages, as well as familial Alzheimer's disease (different mutations in different families). The majority of familial Alzheimer cases, however, are associated with mutations in the PS1 gene (more than 70 different mutations) or the PS2 gene (4 mutations).

Alzheimer Disease↗
PubMed2002

Labeling of cerebral amyloid beta deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice.

UNLABELLED: There is currently no method for noninvasive imaging of amyloid beta (Abeta) deposition in Alzheimer's disease (AD). Because Abeta plaques are characteristic of AD and Abeta deposits contain abundant heparan sulfate proteoglycans that can bind basic fibroblast growth factor (bFGF) and serum amyloid P component (SAP), we investigated a novel route of ligand delivery to the brain to assess Abeta deposition in a transgenic (Tg) mouse model overexpressing Abeta-protein precursor. METHODS: The biodistribution of bFGF injected intranasally was studied using (125)I-bFGF in Tg and wild-type control mice and by unlabeled bFGF and SAP immunocytochemistry with light and electron microscopy. RESULTS: Three- to 5-fold higher amounts of (125)I-bFGF were found in the brain of Tg mice than that of wild-type mice (P < 0.05). bFGF or SAP given intranasally labeled cerebral Abeta plaques in the cortex and microvessels of Tg mice but not in wild-type mice. Weak bFGF staining and no SAP staining were detected in Tg mice without intranasal injection of the ligands. bFGF and SAP stained neurons around the rim of Abeta deposits and throughout the cortex in Tg mice. There was only weak staining of neurons in Tg mice without intranasal injection of bFGF and no staining of SAP in Tg mice without intranasal injection of SAP. No bFGF or SAP staining was evident in wild-type control mice. CONCLUSION: We report a novel noninvasive method for labeling Abeta plaques. This method may be modified for human studies using intranasal injection of radiolabeled ligands and imaging with SPECT or PET.

Administration, Intranasal↗
PubMed2005

[Expression of amyloid beta protein and amyloid precursor protein after focal brain ischemia in human].

OBJECTIVE: To observe the expression of amyloid beta precursor protein and amyloid beta protein in neurons of hippocampal CA1 region after brain ischemia in human. METHODS: Neuronal damage was examined by using HE staining, and expression of APP and Abeta(1-40) was determined by immunohistochemistry in the hippocampal CA1 region of the brain specimens of 43 patients who died 2 h-6 h, 7 h-24 h, 25 h-48 h, 49 h-72 h, 73 h-96 h, 97 h-144 h, or 145 h-168 h after cerebral ischemia and in 2 specimens of patients who died of other diseases as control group. RESULTS: The expression of Abeta(1-40) was 25.07 +/- 2.79 in the specimens 2 h-6 h after cerebral ischemia, peaked 73 h-96 h after cerebral ischemia (33.22 +/- 2.67), then decreased till 145 h-168 h after cerebral ischemia, however, all higher than that in the control group (2.88 +/- 0.18, all P < 0.05). The expression of beta-APP was 33.30 +/- 0.42 2 h-6 h after cerebral ischemia, was 28.11 +/- 2.03 7 h-24 h after cerebral ischemia, increased to peak value (32.32 +/- 1.36) 73 h-96 h after cerebral ischemia, and then decreased to 28.48 +/- 2.01, all higher than that of the control group (25.90 +/- 1.55) with significant differences between those 2 h-6 h and 73 h-96 h after ischemia and that of the control group (both P < 0.01). The increase of beta-APP was positively correlated with the expression of Abeta(1-40) 24 h after ischemia. CONCLUSION: The expression of beta-APP and that of Abeta(1-40) are up-regulated after cerebral ischemia, thus aggravating cerebral ischemia.

Aged↗
PubMed1993

Marked islet amyloid polypeptide-positive amyloid deposition: a possible cause of severely insulin-deficient diabetes mellitus with atrophied exocrine pancreas.

An insulin-deficient 51-year-old man was put on dietary therapy and sulfonylurea (SU). Although there was good glycemic control for 2 years, the fasting blood glucose (FBG) level increased gradually over the subsequent 4-year period, and there was a marked increase in body weight. Secondary failure of SU therapy 20 years after the initial diagnosis led to insulin therapy. The FBG became unstable, and the C-peptide response disappeared. The patient died of nonketotic hyperosmolar coma and pneumonia at the age of 87. At autopsy, the pancreas showed marked atrophy (32 g) with extensive fatty degeneration. Islets replaced by islet amyloid polypeptide (IAPP)-positive amyloid (IAPP-AM) amounted to 77% in the tail, 74% in the body, and 73% in the head of the pancreas. All islets were positive for IAPP-AM throughout the pancreas, except for a pancreatic polypeptide-rich lobe, where none were positive. IAPP-AM-positive islets had also undergone fatty change of the surrounding pancreatic acinar cells. beta-Cells decreased remarkably in number and were displaced to the periphery of the islets by the IAPP-AM deposits. These findings suggest that IAPP-related diabetes could have a progressive course, with secondary oral hypoglycemic agent failure and the subsequent development of severe insulin deficiency similar to that seen in insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1996

Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat.

Recent reports suggest a relationship between traumatic brain injury and the precocious development of neurodegenerative cascades, including diffuse deposits of beta-amyloid peptides (A beta) in the injured brain. Because the lateral fluid-percussion (FP) model of experimental brain injury produces clinically relevant neuropathological sequelae in the rat brain, we used this model together with a series of antibodies specific for amyloid precursor proteins (APPs), APP-like proteins (APLPs), or A beta to identify acute neurodegenerative changes after brain trauma. Male Sprague-Dawley rats were anesthetized and subjected to lateral FP brain injury of moderate to high severity. At 1 hr, 2 hr, 48 hr, 1 week, or 2 weeks after injury, animals were killed and their brains were removed for immunohistochemical analysis. APP/APLP immunoreactivity increased in specific brain regions as early as 1 hr after injury and persisted for at least 2 weeks. Axons in the thalamus and subcortical white matter showed the greatest APP/APLP accumulation. Injured cortex, striatum, cingulum, and hippocampus also demonstrated significant axonal accumulations of APP/APLP. Accumulation of APP/APLPs occurred primarily ipsilateral to the injury, although bilateral changes were observed in some brain regions. No deposition of A beta was observed in any brain region at any time point examined. These results demonstrate a pattern of widespread axonal pathology after lateral FP brain injury in the rat, characterized by intra-axonal accumulations of APP/APLP immunoreactivity in the absence of plaque-like deposits of A beta in the traumatized brain.

Amyloid beta-Peptides↗