Taken together, the characteristics of amyloid plaques in Tg2576 mice are similar to those in Alzheimer's disease with respect to apoE and astrogliosis.
We examined apolipoprotein E (ApoE) immunoreactivity and allele frequency in 12 autopsied cases of progressive supranuclear palsy (PSP), a neurodegenerative disease characterized by diffuse neurofibrillary tangle (NFT) formation without beta-amyloid deposits.
We obtained APOE genotypes, determined diffuse beta-amyloid plaque (A beta P) and Lewy body densities in multiple brain regions, and graded the intensity of CA2-3 ubiquitin-positive neurites, vacuolar change, nigral pathology, amyloid angiopathy, and subpial amyloid deposition.
Several genes involved with AD have been described already, but only the APOE gene on chromosome 19q has been shown to affect the risk of the common late onset form of AD. alpha1-Antichymotrypsin (AACT) is a major component of the amyloid plaques found in the brains of AD patients, and an allele in its gene has been proposed to increase the risk of developing AD when also associated with the APOE-4 allele.
Enhancing ABCA1 activity to reduce ApoE and ABCA1 aggregation is a potential therapeutic strategy for the prevention of ApoE4 aggregation-driven pathology.<b>SIGNIFICANCE STATEMENT</b> ApoE protein plays a key role in the formation of amyloid plaques, a hallmark of Alzheimer's disease (AD).
To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affects neuropathology in aging and Alzheimer's disease (AD), we compared beta-amyloid plaque (A beta P) and neurofibrillary tangle densities, neuropil thread formation, and amyloid angiopathy in five APOE-epsilon 2/3 AD patients, five APOE-epsilon 3/3 AD patients, five APOE-epsilon control patients, and five APOE-epsilon 3/3 control patients.
In a linear regression model, AP percentage area was associated with age (p < 0.0001) and APOE epsilon4 allele (p < 0.0001), but not with CW score (p = 0.70) or gender (p = 0.11).
Several lines of evidence implicate apolipoprotein E (apoE) and its receptor--the low density lipoprotein receptor related protein (LRP)--in Alzheimer's disease (AD) pathogenesis, including increased amyloid deposition in human AD brains of people containing the apoE epsilon 4 allele, presence of apoE and LRP in amyloid plaques, and in vitro uptake of amyloid precursor protein (APP) and amyloid beta protein (A beta) by LRP.
The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype.
These could act either independently or perhaps interact with APOE. alpha 1-Antichymotrypsin (ACT) is a major component of the amyloid plaques found in the brains of AD patients and may play a role in the pathophysiology of AD.
We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer's disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice.
Amyloid-β (Aβ) is derived from the proteolytic processing of amyloid precursor protein (APP), and the deposition of extracellular Aβ to form amyloid plaques is a pathologic hallmark of Alzheimer's disease (AD).
Here, we describe significant CAA in addition to amyloid plaques, in aging APP/Ld transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP) exclusively in neurons.
Models of AD include: aged monkeys that show both cognitive/memory deficits and cellular abnormalities (amyloid deposition/cytoskeletal abnormalities of neurons) in cortex and hippocampus; and Tg mice that express mutant human FAD-linked genes (i.e., APP and PS1) and show increased levels of A.42, amyloid deposits, dystrophic neurites, and local responses of astrocytes and microglia.
The main component of senile plaque amyloid is a 39-to 42-amino-acid segment referred to as beta-amyloid, which is derived from amyloid precursor protein (APP).
Amyloid-β (Aβ) peptides, major components of amyloid plaques and crucial pathogenic molecules in terms of the amyloid hypothesis, are derived from successive proteolytic processing of amyloid-β precursor protein (APP).
Chronic treatment with the α2-adrenoceptor antagonist fluparoxan prevents age-related deficits in spatial working memory in APP×PS1 transgenic mice without altering β-amyloid plaque load or astrocytosis.
We conclude that the simultaneous presence of human mutated Tau(VLW) and plaque-amyloid (and/or APP(SW)) potentiates and anticipates tau phosphorylation at the 12E8 epitope, intensifying pyramidal neuron immunostaining and tau filament formation in this double-transgenic model.
Furthermore, Alzheimer's amyloid precursor protein, which accumulates within the axonal swellings under pathological conditions, co-accumulated with the PrP-amyloid plaques.
To study the effect of amyloid deposits on cell cycle related events in vivo, the expression of cell cycle markers was examined by immunohistochemistry in amyloid precursor protein (APP) transgenic mice (APP23 mice, Swedish double mutation).