Unveiling Resilience to Alzheimer's Disease: Insights From Brain Regional Proteomic Markers

Abstract

Studying proteomics data of the human brain could offer numerous insights into unraveling the signature of resilience to Alzheimer's disease. In our previous study with rigorous cohort selection criteria that excluded 4 common comorbidities, we harnessed multiple brain regions from 43 research participants with 12 of them displaying cognitive resilience to Alzheimer's disease. Based on the previous findings, this work focuses on 6 proteins out of the 33 differentially expressed proteins associated with resilience to Alzheimer's disease. These proteins are used to construct a decision tree classifier, enabling the differentiation of 3 groups: (i) healthy control, (ii) resilience to Alzheimer's disease, and (iii) Alzheimer's disease with dementia. Our analysis unveiled 2 important regional proteomic markers: Aβ peptides in the hippocampus and PA1B3 in the inferior parietal lobule. These findings underscore the potential of using distinct regional proteomic markers as signatures in characterizing the resilience to Alzheimer's disease.

Keywords: Alzheimer’s disease; Proteomics; differential expression; mass spectrometry.

Figure 1.

Proteomic markers that can be used to distinguish HC, ADD, and RAD groups: (a) the decision tree identified 5 proteins, (b) confusion matrix with leave-one-out cross-validation using decision tree classifier, (c) Aβ abundance in HIPP, (d) PA1B3 abundance in IPL, and (e) using Aβ abundance in HIPP and PA1B3 concentration in IPL to distinguish RAD from other groups. (c) and (d) P-values were derived from two-sided Student’s t-tests with the control for multiple hypothesis tests using the Benjamin-Hochberg procedure (FDR = 0.05). Abbreviations: ADD, Alzheimer’s disease with dementia; CAUD, caudate; HC, healthy control; HIPP, hippocampus; IPL, inferior parietal lobule; RAD, resilience to Alzheimer’s disease; SMTG, superior and middle temporal gyrus.