Acta Neuropathology: ADNC-RS is a clinical genetic risk score that predicts Alzheimer's pathology in post-mortem confirmed Parkinson's disease and Louisian dementia.

Alzheimer's disease( AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases that affect more than 6 million people worldwide.
the neuropathological definition of AD is amyloid beta (A beta) plaques and tau nerve fiber tangles (NFT), while PD is the presence of a Lewy small body consisting of alpha-synaptic nucleoproteins (aSyn).
age of patients who received AD clinical diagnosis was about 80 years, while the average age of patients receiving PD clinical diagnosis was between 60 and 60 years old.
growing evidence that AD and PD overlap in pathophysiology in some patients.
In fact, 50-80% of autopsy cases are mainly clinically pathologically diagnosed with Lewy body disease (Lewy body disease, LBD), the most common manifestation of which is PD, accompanied by amyloid beta and tau pathology, which are the main pathological characteristics of AD.
The authors primarily assessed common AD-related genetic variants throughout the genome as predictors of accompanying AD pathology, where the main clinical pathological diagnosis is PD or associated with Louis's dementia (DLB), which is characterized by neuron Louis.
In the first phase of the authors' study, AD neuropathological changes (ADNC) were evaluated in 127 consecutive autopsy-confirmed PD or DLB cases from the same center, and 20 single nucleotide polymorphisms (SNPs) were found to be associated with AD risk.
of these 127 training group individuals, we developed a logistic regression model to predict the existence of ADNC, using reverse step-by-step regression for model selection and ten times cross-validation to evaluate performance.
Best Fit Model generated a risk score for ADNC (ADNC-RS) based on the age of onset and the genotypes of the three SNP (APOE, BIN1, and SORL1 bits), and in our training group, the area under the subject's operating curve (AUC) was 0.751.
the replication phase of the authors' study, they evaluated the performance of the model in a separate test group of 81 genotype individuals.
in the test group, AUC was 0.781, and individuals in the top five of the ADNC-RS were four times more likely to develop AD pathology at the time of the autopsy than each of the two lowest five-fifths groups.
Finally, during the validation phase of the study, the authors applied the ADNC-RS model to 70 LBD individuals from 20 Alzheimer's Research Center (ADRC) with autopsy and genetic data available in the National Alzheimer's Coordination Center (NACC) database.
in this validation group, the AUC is 0.754.
method: Clinical and neuropathological data were evaluated for all autopsy cases registered at the University of Pennsylvania's Neurodegenerative Disease Research Brain Bank Center from February 1985 to July 2019.
clinical pathology diagnosis of each case, mainly determined by neuropathology, followed by the consideration of clinical history.
pathology diagnosis in all cases included in this study is DLB or PD or not accompanied by dementia.
authors ruled out MSA to focus on primary neuron synth nucleocytosis.
208 of the 1922 cases met these criteria, 127 of which had complete genotype data at the beginning of our study, while 81 patients were genotypeded during the study.
, the authors studied 208 PD/DLB cases and confirmed another 70 LBD cases from the multi-site NACC database, proving that the age of onset and the genotype of 3 SNPs were sufficient to identify a group of LBD individuals who were at high risk of developing associated AD pathology.
is important for identifying LBD patients who use amyloid beta or tau as a treatment strategy.
Day, D.L., Tropea, T.F., Robinson, J.L. et al. ADNC-RS, a clinical-genetic risk score, predicts Alzheimer's pathology in autopsy-confirmed Parkinson's disease and Dementia with Lewy bodies. Acta Neuropathol (2020). Source: MedSci Originals !-- Content Presentation Ends -- !-- To Determine If Login Ends.