Insulin resistance, cognition and Alzheimer's disease biomarkers: Evidence that CSF Aβ42 moderates the association between insulin resistance and increased CSF tau levels.

2022-06

Woodfield, Amy

Porter, Tenielle

Gilani, Israa

Noordin, Siti

Li, Qiao-Xin

Collins, Steven

Martins, Ralph N

Maruff, Paul

Masters, Colin L

Rowe, Christopher C

Villemagne, Victor L

Doré, Vincent

Newsholme, Philip

Laws, Simon M

Verdile, Giuseppe

Alzheimer's disease

Amyloid

Biomarkers

Cognitive Function

Insulin Resistance

Tau

Journal Article

0000-0002-8051-0558

0000-0002-6947-9537

0000-0002-5832-9875

0000-0003-3910-2453

0000-0003-3072-7940

0000-0002-5245-6611

0000-0001-8438-3763

10.1016/j.neurobiolaging.2022.03.004

Mounting evidence implicates insulin resistance (IR) with reduced cognition, increased dementia risk and changes in Alzheimer's disease biomarkers. It's unclear how, and at what stage IR has the greatest impact on Alzheimer's disease biomarker progression indicative of cognitive decline. Exploration of potential factors influencing this relationship continue. We have previously reported IR to be associated with cognitive function, and increased CSF tau in a cognitively unimpaired cohort. Now, we aimed to determine if CSF total (t-tau) or phosphorylated tau (p-tau) mediated the relationship between HOMA-IR and cognition, and explore sex or amyloid-β (Aβ) biomarkers as moderators of this relationship. Mediation analysis demonstrated that CSF tau does not directly influence the association between HOMA-IR and cognition. Moderation analysis revealed CSF Aβ42 moderates the relationships between HOMA-IR and CSF tau. The combination of lower CSF Aβ42 and higher HOMA-IR was associated with increases in CSF tau. The CSF Aβ42 moderation finding has potential to be considered when assessing type 2 diabetic risk for tau pathology and cognitive decline.

link

Neurobiology of Aging 2022; 114: 38-48

Neurobiology of Aging