During the last two decades, NPY body fluid concentrations and NPY/PYY brain receptor numbers have been demonstrated to be altered during the course of Alzheimer's disease.
To better understand the biological mechanisms underlying the regulation of AD biomarkers, and its relation to AD, we examined the association between 36 selected single nucleotide polymorphisms (SNPs) and AD biomarkers Aβ1-42, t-tau, and p-tau in CSF in a cohort of 672 samples (571 AD patients and 101 controls) collected within 10 European consortium centers.Our results highlighted five genes, APOE, LOC100129500, PVRL2, SNAR-I, and TOMM40, previously described as main players in the regulation of CSF biomarkers levels, further reinforcing a role for these in AD pathogenesis.
Discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD in CSF by positively classifying controls and AD cases with 96.4% and 95.5% accuracy, respectively.
Aging studies in the senescence-accelerated mouse strain (SAM) prone/8 (SAMP8), an animal model of Alzheimer's disease (AD), revealed significantly decreased mRNA and protein expression of AMF and AMFR in the hippocampus.
Apart from multiple sclerosis, which shares several susceptibility loci with other immune-related disorders, variation at HLA-DRB5 being associated both with Parkinson's disease and Alzheimer's disease, and the association of the C9orf72 repeat expansion with ALS and frontotemporal degeneration, there was little evidence of gene loci being consistently associated with more than one neurological condition or with other conditions.
We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics.