Hypothesis and Theory: Circulating Alzheimer's-Related Biomarkers in Type 2 Diabetes. Insight From the Goto-Kakizaki Rat - Archive ouverte HAL Access content directly
Journal Articles Frontiers in Neurology Year : 2019

Hypothesis and Theory: Circulating Alzheimer's-Related Biomarkers in Type 2 Diabetes. Insight From the Goto-Kakizaki Rat

(1) , (1) , (1) , (1) , (1)
1

Abstract

Epidemiological data suggest an increased risk of developing Alzheimer's disease (AD) in individuals with type 2 diabetes (T2D). AD is anatomically associated with an early progressive accumulation of A beta leading to a gradual Tau hyperphosphorylation, which constitute the main characteristics of damaged brain in AD. Apart from these processes, mounting evidence suggests that specific features of diabetes, namely impaired glucose metabolism and insulin signaling in the brain, play a key role in AD. Moreover, several studies report a potential role of A beta and Tau in peripheral tissues such as pancreatic beta cells. Thus, it appears that several biological pathways associated with diabetes overlap with AD. The link between peripheral insulin resistance and brain insulin resistance with concomitant cognitive impairment may also potentially be mediated by a liver/pancreatic/brain axis, through the excessive trafficking of neurotoxic molecules across the blood-brain barrier. Insulin resistance incites inflammation and pro-inflammatory cytokine activation modulates the homocysteine cycle in T2D patients. Elevated plasma homocysteine level is a risk factor for AD pathology and is also closely associated with metabolic syndrome. We previously demonstrated a strong association between homocysteine metabolism and insulin via cystathionine beta synthase (CBS) activity, the enzyme implicated in the first step of the trans-sulfuration pathway, in Goto-Kakizaki (GK) rats, a spontaneous model of T2D, with close similarities with human T2D. CBS activity is also correlated with DYRK1A, a serine/threonine kinase regulating brain-derived neurotrophic factor (BDNF) levels, and Tau phosphorylation, which are implicated in a wide range of disease such as T2D and AD. We hypothesized that DYRK1A, BDNF, and Tau, could be among molecular factors linking T2D to AD. In this focused review, we briefly examine the main mechanisms linking AD to T2D and provide the first evidence that certain circulating AD biomarkers are found in diabetic GK rats. We propose that the spontaneous model of T2D in GK rat could be a suitable model to investigate molecular mechanisms linking T2D to AD.
Fichier principal
Vignette du fichier
fneur-10-00649.pdf (1.26 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03201562 , version 1 (15-11-2022)

Identifiers

Cite

Jamileh Movassat, Etienne Delangre, Junjun Liu, Yuchen Gu, Nathalie Janel. Hypothesis and Theory: Circulating Alzheimer's-Related Biomarkers in Type 2 Diabetes. Insight From the Goto-Kakizaki Rat. Frontiers in Neurology, 2019, 10, ⟨10.3389/fneur.2019.00649⟩. ⟨hal-03201562⟩
20 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More