SAT366 Expression of Amyloid-related Proteins Associated With Dementia in Polycystic Ovary Syndrome Compared to a Control Population

Disclosure: A.E. Butler: None. A.S. Moin: None. T. Sathyapalan: None. S.L. Atkin: None. Objective: Several risk factors in polycystic ovary syndrome (PCOS) are associated with increased risk for Alzheimer’s disease (AD). We hypothesized that circulatory levels of amyloid-related proteins would be elevated in PCOS but that these would potentially be mitigated by elevated levels of proteins associated with protection from AD. Methods: Somascan proteomic analysis of amyloid-related proteins was undertaken in a well validated PCOS database of 143 women with PCOS and 97 control women. Results: Amyloid-precursor protein (APP) (p<0.05), amyloid P-component (APCS) (p<0.001), apolipoprotein E (apoE) (p<0.01) and apoE3 (p<0.05) were elevated in PCOS, whilst alpha-synuclein (SNCA) (p<0.05) was reduced in PCOS, all features associated with increased AD risk. Correlation analyses of the AD-related proteins with protective heat shock proteins (HSPs) showed that SNCA positively correlated with HSP90 (p<0.01) and with HSP60 (p<0.0001). Correlations with markers of inflammation showed APCS positively correlated with interleukin-6 (IL6) (p<0.05) whilst ApoE and ApoE3 correlated positively with tumor necrosis factor-alpha (TNF-alpha) (p<0.05). Conclusion: The AD-associated protein pattern found in PCOS, with basal elevated APP and reduced SNCA, parallels what has been reported in patients type 2 diabetes. This dysregulated AD-related protein expression in PCOS is likely exacerbated by obesity and insulin resistance-related inflammation and may be modulated by protective HSP mechanisms. Reference: Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Hypoglycaemia in type 2 diabetes exacerbates amyloid-related proteins associated with dementia. Diabetes Obes Metab. 2021 Feb;23(2):338-349. doi: 10.1111/dom.14220. Epub 2020 Oct 25. PMID: 33026133. Presentation Date: Saturday, June 17, 2023