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.
In this report, we demonstrate that transgenic animals that coexpress a FAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish FAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone.
The transmembrane domain and a portion of the C-terminus (A beta) of the amyloid precursor protein, are known to form the nucleus of the amyloid plaque.
Collectively, our results suggest that different pathological mechanisms, namely an intracellular accumulation of APP or extracellular amyloid plaques, may lead to spine abnormalities in young adult APP23 and deltaE9 mice, respectively.
In addition, for animals older than 12 months, we confirmed our previous report that only the two genotypes that form amyloid plaques (APP and PS/APP) have significantly reduced T(2) values compared with NTg controls.
Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system.
A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals.
We developed a cell model of Gerstmann-Sträussler-Scheinker disease, a neurodegenerative condition characterized by PrPM-containing amyloid deposits and neuronal loss, by expressing the Gerstmann-Sträussler-Scheinker haplotype Q217R-129V in human neuroblastoma cells.
Different PrP(sc) "type"-PRNP genotype combinations are found associated with pathological phenotypes that differ in the relative severity of lesions among distinct brain regions, the presence and morphology of certain lesions such as amyloid plaques, and the pattern of intracerebral and tissue deposition of PrP(sc).
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.
Nerve biopsy confirmed amyloid deposits in nerves, and molecular genetic analysis showed a mutation of the transthyretin (V30M) gene for 3 patients; the 2 other patients had acquired amyloidosis.
In both cases, the diagnosis was determined by the detection of amyloid deposits in skin and/or rectal biopsies and identification of TTR mutations by genetic analysis.
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.
Vitreous amyloid deposits are one of the most common ocular manifestations of familial amyloidosis ATTRV30M (FAP-I), which can be the only manifestation of the disease and can appear even after liver transplantation.