Alzheimer’s disease‐related sex differences in insulin sensitivity, glucose metabolism, and spatial memory
Year: 2020
Type: article
Abstract: Background Women are at higher risk for developing Alzheimer’s disease (AD), comprising two‐thirds of AD patients. In this study, we aimed to characterize AD‐related sex differences in insulin sensitivity, glucose tolerance, and spatial learning and memory in male and female APPNL‐F/NL‐F mice, a model of AD, and normal aging C57BL/6 mice. Method Male and female C57BL/6J and APPNL‐F/NL‐F mice underwent data collection at 6 months of age. Insulin and glucose tolerance testing (ITT, GTT) were performed to examine metabolic function, followed by Morris water maze (MWM) to determine cognitive ability. Result Preliminary ITT data (area under the curve for percent change from baseline) indicate that male APPNL‐F/NL‐F mice (n=9; 10,260 ± 679) tended to be less insulin sensitive than genotype‐matched females (n=5; 7,900 ± 494). There were no sex differences observed for C57BL/6 mice and no genotype differences. GTT results support a trend of female C57BL/6 mice (n=7; 9975 ± 1,517) having impaired glucose metabolism compared to genotype‐matched males (n=5; 7,083 ± 584). No sex differences were observed for APPNL‐F/NL‐F mice. Of note, APPNL‐F/NL‐F (n=9; 9,211 ± 1,391) males tended to have impaired glucose metabolism compared to C57BL/6 males. For MWM, female mice tended to have impaired long‐term memory recall as supported by cumulative distance measures (C57BL/6J n=7, 15.24 ± 1.73; APPNL‐F/NL‐F n= 5, 15.61 ± 2.38) and annulus 40 entries normalized for distance swam (C57BL/6J n=7, 0.4833 ± 0.0485; APPNL‐F/NL‐F n=5, 0.4542 ± 0.1174) compared to genotype‐matched males (C57BL/6 n=5, 12.11 ± 1.20; APPNL‐F/NL‐F n=9, 12.03 ± 1.86) (C57BL/6J n=5, 0.6732 ± 0.1128; APPNL‐F/NL‐F n=9, 0.6534 ± 0.1150). Conclusion Preliminary results support insulin insensitivity in male APPNL‐F/NL‐F mice compared to genotype‐matched females and impaired glucose metabolism compared to C57BL/6 males, a potential early indication of AD pathology. Female mice from both genotypes had impaired long‐term memory retrieval compared to genotype‐matched males, possibly providing an insight into female AD pathology. Collectively, these preliminary findings support potential sex differences for insulin sensitivity and long‐term spatial memory in AD pathology. Studies to further elucidate sex differences in AD disease progression are ongoing. This research was supported by the NIH and SIUSOM.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.043146
Institution: SIU Medicine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3112719198