Increased expression of GAPDH in cynomolgus monkeys with spontaneous cognitive decline and amyloidopathy reminiscent of an Alzheimer's‐type disease is reflected in the circulation. Issue 11 (1st July 2021)

• Record Type: Journal Article
• Authors: Darusman, Huda S.; Saepuloh, Uus; Mariya, Sela S.; Sajuthi, Dondin; Schapiro, Steven J.; Hau, Jann
• Other Names: Shively Carol A. guestEditor.; Lacreuse Agnès guestEditor.; Frye Brett M. guestEditor.; Rothwell Emily S. guestEditor.; Moro Manuel guestEditor.
• Is Part Of: American journal of primatology. Volume 83:Issue 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-01
• Subjects: aging -- genes -- neuropathy -- nonhuman primate -- spontaneous model; Primates -- Periodicals; Primates -- Périodiques; 599.8
• DOI: 10.1002/ajp.23296
• Languages: English
• ISSNs: 0275-2565

Abstract

Abstract: Previous studies of aging cynomolgus monkeys from our group identified spontaneous age‐associated cognitive declines associated with biomarkers and brain lesions reminiscent of Alzheimer's Disease (AD), in a proportion of aged monkeys. However, the molecular mechanisms that underlie the spontaneous amyloid disorders and cognitive declines observed in these affected monkeys have yet to be investigated in detail. Using reverse transcriptase quantitative real time PCR techniques, normalized to the ACTB housekeeping gene, we analyzed the expression patterns of a number of genes which have been implicated in amyloid and tau abnormalities, in well‐characterized aged cynomolgus monkeys with cognitive decline. A significantly increased expression of the genes coding for glyceraldehyde 3‐phosphate dehydrogenase (GAPDH), was found in aged‐cognitive decline monkeys compared to age‐matched healthy controls. GAPDH has been implicated in several neurodegenerative diseases and interacts with beta amyloid precursor proteins. These findings provide support for the utilization of cynomolgus macaques in translational preclinical research as valid spontaneous models in experimental investigations of the relationships among aging, cognitive decline, and the neuropathy of AD. Abstract : RESEARCH HIGHLIGHTS: Previous behavioral studies from our group identified age‐associated cognitive declines associated with biomarkers and brain pathology reminiscent of Alzheimer's Disease (AD) in a proportion of aging cynomolgus monkeys. There are three genes that show significant expression (MIQE guidelines; glyceraldehyde 3‐phosphate dehydrogenase [GAPDH], APH1A, and ADAM10), with GAPDH the only gene that is expressed statistically significantly higher in aged subjects with cognitive decline The expression pattern of the GAPDH gene and other genes in our subjects may begin to illuminate a molecular mechanism of amyloid precursor protein progression that may be related to the cognitive performance of aged cynomolgus monkeys, and these findings provide support for relationships among aging, cognitive decline, and the neuropathy of AD.