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).
In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Sträussler-Scheinker disease (GSS).
Transcript levels of the genes associated with loss of synaptic plasticity (Bdnf, Syn, GluN1, α7-nAChR, and M<sub>1</sub>-mAChR), formation of neurofibrillary tangles (Tau4 and Tau3), and amyloid plaques (App, Adam10, and Bace1), in the hippocampus of rats at 0, 1, 3, 6, and 9 days after ODX (D<sub>0</sub>, D<sub>1</sub>, D<sub>3</sub>, D<sub>6</sub> and D<sub>9</sub>, respectively) were determined.
Using immunohistochemistry, AGEs, CML, and RAGE were found within amyloid deposits, more commonly in AA amyloid than in AL amyloid and not in ATTR amyloid.
Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression.
Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression.
Using logistic regression models, we analyzed associations of Meth with cerebral gliosis (immunohistochemistry for ionized calcium-binding adapter molecule-1 (Iba1) and glial fibrillary acidic protein (GFAP) in frontal, temporo-parietal, and putamen-internal capsule regions), synaptodendritic loss (confocal microscopy for synaptophysin (SYP) and microtubule-associated protein-2 (MAP2) in frontal cortex), β-amyloid plaque deposition (immunohistochemistry in frontal and temporo-parietal cortex and putamen), and arteriolosclerosis (histopathology in forebrain white matter).
Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.
Amyloid subtyping using laser capture microdissection and mass spectrometry-based proteomic analysis did not identify ANO5 or any fragment of ANO5 in the amyloid deposits, but detected other known amyloidogenic proteins.
Serum amyloid P component (SAP), a highly conserved plasma protein named for its universal presence in amyloid deposits, is the single normal circulating protein that shows specific calcium-dependent binding to DNA and chromatin in physiological conditions.
Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects.
Amyloid deposits in the proband, one of the transplanted individuals, were composed of apolipoprotein A-I (apoA-I), and among living family members there was complete concordance between amyloidosis and the presence of a novel 9 base pair in-frame deletion mutation in exon 4 of the apoA-I gene, causing a loss of residues Glu70Phe71Trp72.
The lipid-dependent polymorphisms exhibited by apoC-II fibrils could determine the properties of apoC-II in renal amyloid deposits and their potential role in the development of cardiovascular disease.
An increased expression of GMF in APs and neurofibrillary tangles in the AD brain, and the co-localization of GMF and ApoE4 in APs suggest that GMF and ApoE4 together should be contributing to the neuropathological changes associated with AD.
In this model, AP formation does not depend on [Aβ]c. The present interpretation of the AH, unifying the pathogenetic theories for IAD and NIAD, will explain why AP and APOE4 may be observed in healthy aging and why they are not the cause of AD.
We designed our approach based on neuropathological characteristics of AD to investigate apoE levels in relation to the APOE genotype and AD-related neurofibrillary changes, and amyloid deposits.