PMID- 31293498
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 10
DP  - 2019
TI  - Hypothesis and Theory: Circulating Alzheimer's-Related Biomarkers in Type 2 
      Diabetes. Insight From the Goto-Kakizaki Rat.
PG  - 649
LID - 10.3389/fneur.2019.00649 [doi]
LID - 649
AB  - 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 Abeta 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 Abeta 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.
FAU - Movassat, Jamileh
AU  - Movassat J
AD  - Univ Paris Diderot-Sorbonne Paris Cite, Laboratoire de Biologie et Pathologie du 
      Pancreas Endocrine, Unite de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 
      CNRS, Paris, France.
FAU - Delangre, Etienne
AU  - Delangre E
AD  - Univ Paris Diderot-Sorbonne Paris Cite, Laboratoire de Biologie et Pathologie du 
      Pancreas Endocrine, Unite de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 
      CNRS, Paris, France.
FAU - Liu, Junjun
AU  - Liu J
AD  - Univ Paris Diderot-Sorbonne Paris Cite, Laboratoire de Biologie et Pathologie du 
      Pancreas Endocrine, Unite de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 
      CNRS, Paris, France.
FAU - Gu, YuChen
AU  - Gu Y
AD  - Univ Paris Diderot-Sorbonne Paris Cite, Laboratoire Processus Degeneratifs, 
      Stress et Vieillissement, Unite de Biologie Fonctionnelle et Adaptative (BFA), 
      UMR 8251 CNRS, Paris, France.
FAU - Janel, Nathalie
AU  - Janel N
AD  - Univ Paris Diderot-Sorbonne Paris Cite, Laboratoire Processus Degeneratifs, 
      Stress et Vieillissement, Unite de Biologie Fonctionnelle et Adaptative (BFA), 
      UMR 8251 CNRS, Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20190626
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC6606723
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - BDNF
OT  - Dyrk1A
OT  - GK rat
OT  - diabetes
OT  - plasma biomarkers
OT  - tau
EDAT- 2019/07/12 06:00
MHDA- 2019/07/12 06:01
PMCR- 2019/06/26
CRDT- 2019/07/12 06:00
PHST- 2019/03/06 00:00 [received]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/07/12 06:00 [entrez]
PHST- 2019/07/12 06:00 [pubmed]
PHST- 2019/07/12 06:01 [medline]
PHST- 2019/06/26 00:00 [pmc-release]
AID - 10.3389/fneur.2019.00649 [doi]
PST - epublish
SO  - Front Neurol. 2019 Jun 26;10:649. doi: 10.3389/fneur.2019.00649. eCollection 
      2019.