TY - JOUR
T1 - Neuropathological links between T2DM and LOAD
T2 - systematic review and meta-analysis
AU - Lemche, Erwin
AU - Hortobágyi, Tibor
AU - Kiecker, Clemens
AU - Turkheimer, Federico
PY - 2025/3/10
Y1 - 2025/3/10
N2 - Recent decades have described in-parallel neuropathological mechanisms, increasing the risk for developing late-onset Alzheimer's dementia (LOAD) in type 2 diabetes mellitus (T2DM), however, still little is known of the role of diabetic encephalopathy and brain atrophy in LOAD. The aim of this systematic review is to provide a comprehensive view on diabetic encephalopathy/cerebral atrophy, taking into account neuroimaging data, neuropathology, metabolic and endocrine mechanisms, amyloid formation, brain perfusion impairments, neuroimmunology and inflammasome activation. Identified were key switches, to further meta-analyse genomic candidate loci and epigenetic modifications. For the qualitative meta-analysis of genomic bases extracted, human linkage studies were examined; for epigenetic mechanisms, data from both human and animal studies were described. For the systematic review of pathophysiological mechanisms, 1259 publications were evaluated, and 93 gene loci extracted for candidate risk linkages. 66 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlighted the insulin signalling system, vascular markers, inflammation and inflammasome pathways, amylin interactions, and glycosylation mechanisms. The protocol was registered with PROSPERO (ID: CRD42023440535).
AB - Recent decades have described in-parallel neuropathological mechanisms, increasing the risk for developing late-onset Alzheimer's dementia (LOAD) in type 2 diabetes mellitus (T2DM), however, still little is known of the role of diabetic encephalopathy and brain atrophy in LOAD. The aim of this systematic review is to provide a comprehensive view on diabetic encephalopathy/cerebral atrophy, taking into account neuroimaging data, neuropathology, metabolic and endocrine mechanisms, amyloid formation, brain perfusion impairments, neuroimmunology and inflammasome activation. Identified were key switches, to further meta-analyse genomic candidate loci and epigenetic modifications. For the qualitative meta-analysis of genomic bases extracted, human linkage studies were examined; for epigenetic mechanisms, data from both human and animal studies were described. For the systematic review of pathophysiological mechanisms, 1259 publications were evaluated, and 93 gene loci extracted for candidate risk linkages. 66 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlighted the insulin signalling system, vascular markers, inflammation and inflammasome pathways, amylin interactions, and glycosylation mechanisms. The protocol was registered with PROSPERO (ID: CRD42023440535).
U2 - 10.1152/physrev.00040.2024
DO - 10.1152/physrev.00040.2024
M3 - Review article
C2 - 40062731
SN - 0031-9333
JO - Physiological Reviews
JF - Physiological Reviews
ER -