Amylin as a potential link between type 2 diabetes and alzheimer disease

• Published in: Annals of neurology Vol. 86; no. 4; pp. 539 - 551
• Main Authors: Martinez‐Valbuena, Ivan, Valenti‐Azcarate, Rafael, Amat‐Villegas, Irene, Riverol, Mario, Marcilla, Irene, Andrea, Carlos E., Sánchez‐Arias, Juan Antonio, Mar Carmona‐Abellan, Maria, Marti, Gloria, Erro, Maria‐Elena, Martínez‐Vila, Eduardo, Tuñon, Maria‐Teresa, Luquin, Maria‐Rosario
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2019; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer's disease; Amylin; Amyloid beta-Peptides - metabolism; Amyloidogenesis; Beta cells; Brain; Brain - metabolism; Case-Control Studies; Dementia disorders; Deposits; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Etiology; Female; Humans; Inclusions; Insulin; Islet Amyloid Polypeptide - metabolism; Male; Middle Aged; Neurodegenerative diseases; Neuropathology; Pancreas; Pancreas - metabolism; Pathogenesis; Proteins; Retrospective Studies; Tau protein; tau Proteins - metabolism
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.25570

Objective Alzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and β‐amyloid (Aβ) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients. Methods We studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD. We examined Aβ and tau accumulation in the pancreas as well as that of amylin in the brain. Moreover, we performed proximity ligation assays to ascertain whether tau and/or Aβ interact with amylin in either the pancreas or brain of these subjects. Results Cytoplasmic tau and Aβ protein deposits were detected in pancreatic β cells of subjects with AD as well as in subjects with a normal neuropathological examination but with a history of T2DM and in a small cohort of control subjects without T2DM. Furthermore, we found amylin deposits in the brain of these subjects, providing histological evidence that amylin can interact with Aβ and tau in both the pancreas and hippocampus. Interpretation The presence of both tau and Aβ inclusions in pancreatic β cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD. ANN NEUROL 2019;86:539–551