This study investigated whether the Alzheimer’s disease (AD) pathological lesions diffuse plaques (DPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs). For this study, downregulation of brain-derived neurotrophic factor (BDNF) and its cognate neurotrophin receptor, TrkB, were observed during the progression of dementia. They performed negative binomial (NB) regressions using gene expression data accrued from a single population of CA1 pyramidal neurons and regional hippocampal dissections obtained from participants in the Rush Religious Orders Study (RROS). The RROS participants included older religious clergy who have agreed to medical and psychological evaluation each year and brain donation after death. This study began in 1993 and has enrolled more than 1,100 participants across the United States. The study has 22 years of clinical data on more than 1,100 people and brain tissue from over 350 people. The dataset includes gene expression, microarray, and neuropathological data. The data revealed that BDNF and TrkB dysregulation contribute to AD neuropathology, most notably hippocampal NPs and NFTs.