Abstract
Increased risks for Alzheimer's disease (AD) are a well-recognized consequence of diabetes, insulin resistance (IR), and hyperinsulinemia. Since cerebrospinal fluid (CSF) is surrounding the central nervous system, alterations of β-amyloid (Aβ) and tau protein in the CSF may be indicative of AD-type degenerations in the brain. Current laboratory diagnosis of AD uses three biomarkers in CSF: Aβ1-42, total tau (t-Tau), and phosphorylated tau (p-Tau). However, changes in these biomarkers in diabetic and prediabetic patients are scattered and variable in literature. Thus, we attempt to perform a systematical analysis of these available data. MEDLINE, EMBASE, the Cochrane Central database, China National Knowledge Infrastructure (CNKI), and Wanfang Data electronic databases were searched to gather published studies that have evaluated the AD-type biomarkers in the CSF of subjects with diabetes, IR, or hyperinsulinemia in comparison with respective controls. Overall analysis of the published data showed no significant differences in Aβ1-42, t-Tau, and p-Tau levels in the CSF between the (pre)diabetic subjects and controls. However, subgroup analysis suggested that (pre)diabetic conditions might accelerate decrease of Aβ1-42, but increase of t-Tau levels in the CSF of subjects with cognitive impairment, and the association with p-Tau in the CSF was stronger (P = 0.001) for diabetes than those of prediabetes (P = 0.61). Our analyses reveal that the relationship between (pre)diabetic conditions and AD-type biomarker status in the CSF was subjective to clinical characteristics.
Highlights
Diabetes represents a group of metabolic disorders caused by impaired insulin signaling and function
The Alzheimer’s disease (AD) is the most common type of dementia, characterized by two pathological hallmarks including formation of senile plaques (SPs) by extracellular deposits of β-amyloid (Aβ) and intracellular neurofibrillary tangles (NFT) from aggregated hyperphosphorylated Tau proteins in the brain (Jack et al, 2013), which are associated with elevated levels of phosphorylated Tau (p-Tau) and decreased levels of the nonsoluble Aβ1-42 from abnormal cleavage of Aβ in the cerebrospinal fluid (CSF) (Blennow and Hampel, 2003)
The search terms and key words included “diabetes,” “Alzheimer,” “insulin,” “cerebrospinal fluid,” “amyloid,” “tau,” and “dementia.” These key words were combined with type 2 diabetes (T2D), type 2 diabetes mellitus (T2DM), type 1 diabetes (T1D), type 1 diabetes mellitus (T2DM), insulin resistance (IR), hyperinsulinemia, hyperglycemia, glucose, glycemia, impaired glycemia, ApoE, duration, complications, and treatment modality to locate studies ondiabetes and associated variables
Summary
Diabetes represents a group of metabolic disorders caused by impaired insulin signaling and function. Mounting evidences from longitudinal and cross-sectional studies as well as biological research have demonstrated a significant association between diabetes and increased risks of multiple-domain cognitive decline and even dementia (McCrimmon et al, 2012). The AD is the most common type of dementia, characterized by two pathological hallmarks including formation of senile plaques (SPs) by extracellular deposits of β-amyloid (Aβ) and intracellular neurofibrillary tangles (NFT) from aggregated hyperphosphorylated Tau proteins in the brain (Jack et al, 2013), which are associated with elevated levels of phosphorylated Tau (p-Tau) and decreased levels of the nonsoluble Aβ1-42 from abnormal cleavage of Aβ in the cerebrospinal fluid (CSF) (Blennow and Hampel, 2003). We collected data from published case–control studies of diabetes, prediabetes, and CSF biomarkers, and performed a meta-analysis to help clarify the association between diabetes or prediabetes and CSF biomarkers of neurodegeneration implicated in the development of AD
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