Potential Alzheimer's early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology.

TitlePotential Alzheimer's early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology.
Publication TypeJournal Article
Year of Publication2024
AuthorsWallace CH, Oliveros G, Xie L, Serrano P, Rockwell P, Figueiredo-Pereira M
JournalSci Rep
Volume14
Issue1
Pagination3730
Date Published2024 Feb 14
ISSN2045-2322
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Biomarkers, Chalcones, Diazoxide, Disease Models, Animal, Female, Rats, Rats, Inbred F344, Rats, Transgenic, Spatial Memory
Abstract

Alzheimer's disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer's model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings.

DOI10.1038/s41598-024-54156-z
Alternate JournalSci Rep
PubMed ID38355687
PubMed Central IDPMC10867006
Grant ListR25GM060665 / GF / NIH HHS / United States