The Alzheimer Link to Neurodegeneration in Diabetes

Type 2 diabetes mellitus (T2DM) is associated with many health problems, but new research out of Monash University in Australia suggests that it can also promote neurodegeneration similar to the damage that occurs in Alzheimer disease (AD).¹

Similar to AD, diabetes is unfortunately on the rise, with 25.8 million people diagnosed in the United States in 2010 and 29.1 million in 2012. T2DM is the most common form. The excess sugar than remains in the blood of people with diabetes can damage organs and wreak havoc on bodily systems. There is increased risk for hypertension, heart attack, stroke, and blindness, as well as numerous other health issues. It is not at all surprising that central nervous system damage and neuronal death might also result.

Led by Chris Moran of the Stroke and Ageing Research Group in the Department of Medicine, Monash University, the researchers sought to understand whether T2DM can cause brain damage in a similar manner as AD, specifically by promoting the deposition of brain β-amyloid or tau. Both of these proteins are found in AD brain and are believed to contribute to neurodegeneration.

The scientists used neuroimaging to study 816 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The ADNI is an organization formed by the National Institutes of Health (NIH) in 2004. The goal of the ADNI is to use biomarkers to detect AD at earlier stages. It currently consists of government and private sponsors.

In the present study, participants had diagnoses of AD dementia, mild cognitive impairment or they had normal cognition. The investigators measured cortical thickness, brain β-amyloid load, and cerebrospinal fluid (CSF levels) of β-amyloid and tau. All study subjects underwent magnetic resonance imaging (MRI). Some also received brain β-amyloid imaging (n = 102) and others were assessed via CSF Aβ and tau measurements (n = 415).

A total of 124 people from the ADNI sample had T2DM and 692 did not. People with T2DM had significantly lower cortical thickness in the bilateral frontal and parietal regions. T2DM was also associated with significantly more CSF total tau and phosphorylated tau. Phosphorylated tau is the form associated with AD.

In their report, the research group concluded that “T2DM may promote neurodegeneration independent of AD dementia diagnosis, and its effect may be driven by tau phosphorylation. The mechanisms through which T2DM may promote tau phosphorylation deserve further study.”

Interestingly, other research has previously supported the AD T2DM link, for example, β-amyloid autoantibodies were elevated in the blood serum of people with T2DM in a study of 92 individuals with T2DM compared to age-matched healthy control participants.² β-amyloid autoantibodies positively correlated with cholesterol levels, low density lipoprotein cholesterol, and triglycerides. The investigators concluded that β-amyloid autoantibodies might actually be used clinically as a biomarker to help diagnose AD.

Overall, the link between T2DM and AD appears to be increasingly supported. Control of T2DM through lifestyle interventions and medical treatments could greatly reduce the risk of dementia and neurodegeneration, in addition to reducing the risk of numerous other medical problems.

Key Points

• T2DM is associated with lower cortical thickness and significantly more CSF total tau and phosphorylated tau.

• β-amyloid autoantibodies are elevated in the blood serum of people with T2DM.

• T2DM and AD appear to share perturbations of tau, β-amyloid and increases in neurodegeneration.

References:

1. Moran C, et al. Type 2 diabetes mellitus and biomarkers of neurodegeneration. Neurology. 2015 Sep 2. [Epub ahead of print]

2. Kim I, et al. A relationship between Alzheimer's disease and type 2 diabetes mellitus through the measurement of serum amyloid-beta autoantibodies. J Alzheimers Dis. 2010;19(4):1371-1376.