The role of type 2 diabetes in neurodegeneration.
A growing body of evidence links type-2 diabetes (T2D) with dementia and neurodegenerative diseases such as Alzheimer's disease (AD). AD is the most common form of dementia and is characterised neuropathologically by the accumulation of extracellular beta amyloid (Aβ) peptide aggregates and intracellular hyper-phosphorylated tau protein, which are thought to drive and/or accelerate inflammatory and oxidative stress processes leading to neurodegeneration. Although the precise mechanism remains unclear, T2D can exacerbate these neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism and CNS insulin resistance are features of both AD and T2D. Cell culture and animal studies have indicated that the early accumulation of Aβ may play a role in CNS insulin resistance and impaired insulin signalling. From the viewpoint of insulin resistance and impaired insulin signalling in the brain, these are also believed to initiate other aspects of brain injury, including inflammatory and oxidative stress processes. Here we review the clinical and experimental pieces of evidence that link these two chronic diseases of ageing, and discuss underlying mechanisms. The evaluation of treatments for the management of diabetes in preclinical, and clinical studies and trials for AD will also be discussed.
School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Bentley, Western Australia 6102, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
Giuseppe
G
Verdile
Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
Stephanie J
SJ
Fuller
School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Bentley, Western Australia 6102, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia. Electronic address: r.martins@ecu.edu.au.
Ralph N
RN
Martins
D000818:Animals; D001921:Brain / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*
Alzheimer's disease; Amylin; Beta amyloid; Diabetes; Neurodegeneration; Tau