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.
Misfolded and abnormal β-sheets forms of wild-type proteins, such as cellular prion protein (PrP<sup>C</sup>) and amyloid beta (Aβ), are believed to be the vectors of neurodegenerative diseases, prion and Alzheimer's disease (AD), respectively.
In this research paper, our aim is to evaluate the association between the APOE, CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive impairment (MCI).
The cell-to-cell transmission of the major pathogenic proteins of Parkinson's disease and Alzheimer's disease is reminiscent of the prion protein, which is defined as a proteinaceous infectious particle that causes human and animal transmissible spongiform encephalopathies.
The initial report that cellular prion protein (PrP<sup>C</sup>) mediates toxicity of amyloid-β species linked to Alzheimer's disease was initially treated with scepticism, but growing evidence supports this claim.
Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease.
Fyn is an attractive target for AD therapeutics, not only based on its activation by Aβ via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD.
Cellular prion protein (PrP<sup>C</sup>) binds the scrapie conformation of PrP (PrP<sup>Sc</sup>) and oligomeric β-amyloid peptide (Aβo) to mediate transmissible spongiform encephalopathy (TSE) and Alzheimer's disease (AD), respectively.
The Aβ deposition in the grey matter was typical of that seen in Alzheimer's disease and Aβ in the blood vessel walls was characteristic of cerebral amyloid angiopathy and did not co-localize with prion protein deposition.
To test the sensitivity and the specificity of our method we also purified PrP from 20, 50 and 100 mg of cerebral cortical tissues taken from six frozen CJD brains and one Alzheimer's disease brain of our collection.
ADAM10, a disintegrin and metalloprotease that plays a key role in the pathogenesis of Alzheimer's disease, was recently shown to use PrP(c) as a substrate.
Our findings suggest that strategies targeting the interaction between PrP and OC-positive oligomers, which have been shown to be highly concentrated in the vicinity of amyloid plaques, may have therapeutic potential against Alzheimer's disease.
These findings support a critical role for cellular prion protein in the deleterious synaptic actions of extracellular soluble tau in tauopathies, including Alzheimer's disease.