Possible significance of aFGF-positive astrocytes in the surroundings of the senile plaque will be discussed in relation to receptor mediated or non-mediated mechanisms.
A constituent of senile plaques in AD is beta-amyloid, a hydrophobic peptide of 39-43 amino acids and a fragment of the amyloid precursor protein (APP).
These findings suggest that the interaction of ApoE with tau and amyloid-beta proteins in AD could play a important role in the formation of NFT and SP, respectively, contributing to the pathogenesis of AD.
In apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE epsilon 3, suggesting increased probability of SP initiation.
Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque.
Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque.
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.
AD cases with larger numbers of neurofibrillary tangles had higher levels of GFAP transcript; AD cases with larger numbers of senile plaques had higher levels of APP695 transcript.
Neuritic plaques characteristic of AD were once thought to be exclusively associated with beta-A4 amyloid; however, some pedigrees with familial prion disease produced neuritic plaques with PrP amyloid cores.
In some places plaques bore a resemblance to senile neuritic plaques and in the hippocampus there were abundant typical neuritic plaques giving positive staining reactions for beta-amyloid protein and tau protein, but not PrP.
The main constituent of senile plaques is amyloid beta-peptide (A beta) and in recent years, pathogenic mutations in the amyloid precursor protein (APP) gene have been discovered in some AD families.
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.
Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects.
One of the most prominent pathological characteristics is beta A4 amyloid deposition in senile plaques in the brain parenchyma and in cerebral blood vessels. beta A4 amyloid is processed from a larger integral membrane protein, the beta A4 amyloid precursor protein.