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Type 2 diabetes may promote neurodegeneration independent of Alzheimer's disease

Cross-sectional analysis of the Alzheimer’s Disease Neuroimaging Initiative study cohort suggests type 2 diabetes may encourage neurodegeneration independent of Alzheimer’s disease dementia, and may be driven by tau phosphorylation.

“Type 2 diabetes mellitus is associated with a nearly 2-fold increased incident risk of dementia and [Alzheimer’s] disease dementia,” Chris Moran, MBBCh, of the Stroke and Aging Research Group at Monash University in Melbourne, Australia, and colleagues wrote. “Recently, we demonstrated that the association between [type 2 diabetes] and cognitive impairment in older age may primarily be driven by brain atrophy rather than cerebrovascular brain lesions, and that this atrophy occurs in cortical regions similar to those affected in [Alzheimer’s disease] dementia. However, there are limited data available from in vivo studies to determine whether [type 2 diabetes] contributes to the accumulation of [Alzheimer’s disease] pathology.”

Researchers assessed cross-sectional associations between type 2 diabetes and cortical thickness, brain β-amyloid load and cerebrospinal fluid levels of β-amyloid and tau among individuals with diagnosed Alzheimer’s disease dementia, mild cognitive impairment and normal cognition. All study participants (n = 816) underwent MRI and a subsample underwent brain amyloid imaging (n = 102) and cerebrospinal fluid β-amyloid and tau measurements (n = 415).

Overall, 124 individuals had type 2 diabetes.

When adjusting for age, sex, total intracranial volume, APO ε4 status and cognitive diagnosis, type 2 diabetes was associated with greater cerebrospinal fluid total tau (P = .04) and phosphorylated tau (P = .02).

The inclusion of phosphorylated tau attenuated the association between type 2 diabetes and cortical thickness by 15%, according to researchers.

“In addition to confirming prior findings that [type 2 diabetes] is associated with brain atrophy, we now demonstrate for the first time, a strong relationship between [type 2 diabetes] and the amount of [phosphorylated]-tau in the [cerebrospinal fluid]. We did not find evidence of a significant relationship between [type 2 diabetes mellitus] and brain or [cerebrospinal fluid] Aβ levels,” Moran and colleagues wrote. “In all, our findings suggest that the neurodegenerative effects of [type 2 diabetes] may be independent and possibly additive to those of [Alzheimer’s disease], and driven by pathways that promote neuronal tau more than Aβ.” – by Amanda Oldt

Disclosure: Moran reports receiving an Alzheimer’s Australia Dementia Research Foundation scholarship. Please see the full study for a list of all authors’ relevant financial disclosures.