eprintid: 10069667 rev_number: 21 eprint_status: archive userid: 608 dir: disk0/10/06/96/67 datestamp: 2019-03-06 09:20:53 lastmod: 2021-10-05 00:32:41 status_changed: 2019-03-06 09:20:53 type: article metadata_visibility: show creators_name: Hoscheidt, SM creators_name: Starks, EJ creators_name: Oh, JM creators_name: Zetterberg, H creators_name: Blennow, K creators_name: Krause, RA creators_name: Gleason, CE creators_name: Puglielli, L creators_name: Atwood, CS creators_name: Carlsson, CM creators_name: Asthana, S creators_name: Johnson, SC creators_name: Bendlin, BB title: Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: APOE ɛ4, CSF AD biomarkers, insulin resistance, memory function note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: BACKGROUND: Type 2 diabetes is associated with an increased risk for Alzheimer’s disease (AD). Regulation of normal insulin function may be important in reducing the prevalence of dementia due to AD, particularly in individuals who harbor genetic risk for or have a parental family history of AD. The relationship between insulin resistance (IR) and AD pathology remains poorly understood, particularly in midlife prior to the onset of clinical metabolic disease or cognitive decline. // OBJECTIVE: We examined associations between IR as indexed by HOMA-IR, cerebrospinal fluid (CSF) biomarkers of AD pathology, and memory in middle-aged adults enriched for AD. We postulated that higher HOMA-IR and APOE ɛ4 carriage would be associated with greater CSF AD pathology and poor memory performance. // METHODS: Cognitively asymptomatic middle-aged adults (N = 70, mean age = 57.7 years) from the Wisconsin Alzheimer’s Disease Research Center with a parental family history of dementia due to AD underwent lumbar puncture, blood draw, and neuropsychological testing. CSF AD biomarkers including soluble amyloid-β protein precursor β (sAβPPβ), amyloid-β42 (Aβ42), and phosphorylated tau (P-tau181) were examined with respect to HOMA-IR and APOE ɛ4 status. Delayed memory performance was examined with respect to HOMA-IR, CSF AD biomarkers, and APOE ɛ4 status. // RESULTS: Higher HOMA-IR was associated with higher sAβPPβ and Aβ42 . APOE ɛ4 carriers had significantly higher levels of sAβPPα, sAβPPβ, and P-tau181/Aβ42 compared to noncarriers. The concurrent presence of higher HOMA-IR and CSF AD pathology predicted worse delayed memory performance. // CONCLUSION: Overall, the findings suggest that IR and APOE ɛ4 are contributing factors to the development of AD pathology in midlife, and provide support for targeting insulin function as a potentially modifiable risk factor for AD. date: 2016 date_type: published publisher: IOS PRESS official_url: https://doi.org/10.3233/JAD-160110 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1125726 doi: 10.3233/JAD-160110 language_elements: English lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Novi, Maya actors_id: MNOVI52 actors_role: owner full_text_status: public publication: Journal of Alzheimer's Disease volume: 52 number: 4 pagerange: 1373-1383 pages: 11 issn: 1875-8908 citation: Hoscheidt, SM; Starks, EJ; Oh, JM; Zetterberg, H; Blennow, K; Krause, RA; Gleason, CE; ... Bendlin, BB; + view all <#> Hoscheidt, SM; Starks, EJ; Oh, JM; Zetterberg, H; Blennow, K; Krause, RA; Gleason, CE; Puglielli, L; Atwood, CS; Carlsson, CM; Asthana, S; Johnson, SC; Bendlin, BB; - view fewer <#> (2016) Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults. Journal of Alzheimer's Disease , 52 (4) pp. 1373-1383. 10.3233/JAD-160110 <https://doi.org/10.3233/JAD-160110>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10069667/3/Hoscheidt_Insulin%20Resistance%20is%20Associated%20with%20Increased%20Levels%20of%20Cerebrospinal%20Fluid%20Biomarkers%20of%20Alzheimer%27s%20Disease.pdf