Neuropathological links between T2DM and LOAD: systematic review and meta-analysis.

Area of Science:

• Neuroscience
• Endocrinology
• Genetics

Background:

• Type 2 diabetes mellitus (T2DM) is increasingly linked to late-onset Alzheimer's dementia (LOAD).
• The specific roles of diabetic encephalopathy and brain atrophy in LOAD pathogenesis remain under-explored.
• Understanding these connections is crucial for identifying shared risk mechanisms.

Purpose of the Study:

• To systematically review and synthesize current knowledge on diabetic encephalopathy and cerebral atrophy in the context of LOAD.
• To analyze neuroimaging, neuropathological, metabolic, endocrine, and immunological factors.
• To perform meta-analyses of genomic loci and epigenetic modifications.

Main Methods:

• Systematic review of 1,259 publications on pathophysiological mechanisms.
• Qualitative meta-analysis of 93 extracted gene loci from human linkage studies.
• Evaluation of 66 publications for genomic association and epigenomic modifications in human and animal studies.

Main Results:

• Key pathophysiological pathways identified include insulin signaling, vascular markers, inflammation, inflammasome activation, amylin interactions, and glycosylation.
• Genomic analysis highlighted candidate risk loci.
• Epigenetic modifications were also examined.

Conclusions:

• Insulin signaling, vascular dysfunction, inflammation, and aberrant protein interactions are central to the T2DM-LOAD link.
• Further research into these shared mechanisms can inform therapeutic strategies for both conditions.
• This review provides a comprehensive overview of the complex interplay between T2DM and LOAD neuropathology.