PMID- 19885299
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20091215
LR  - 20220409
IS  - 1932-2968 (Electronic)
IS  - 1932-2968 (Linking)
VI  - 2
IP  - 6
DP  - 2008 Nov
TI  - Alzheimer's disease is type 3 diabetes-evidence reviewed.
PG  - 1101-13
AB  - Alzheimer's disease (AD) has characteristic histopathological, molecular, and 
      biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; 
      dystrophic neurites; amyloid precursor protein, amyloid-beta (APP-Abeta) 
      deposits; increased activation of prodeath genes and signaling pathways; impaired 
      energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA 
      damage. Gaining a better understanding of AD pathogenesis will require a 
      framework that mechanistically interlinks all these phenomena. Currently, there 
      is a rapid growth in the literature pointing toward insulin deficiency and 
      insulin resistance as mediators of AD-type neurodegeneration, but this surge of 
      new information is riddled with conflicting and unresolved concepts regarding the 
      potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, 
      and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM 
      causes brain insulin resistance, oxidative stress, and cognitive impairment, but 
      its aggregate effects fall far short of mimicking AD; (2) extensive disturbances 
      in brain insulin and insulin-like growth factor (IGF) signaling mechanisms 
      represent early and progressive abnormalities and could account for the majority 
      of molecular, biochemical, and histopathological lesions in AD; (3) experimental 
      brain diabetes produced by intracerebral administration of streptozotocin shares 
      many features with AD, including cognitive impairment and disturbances in 
      acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with 
      insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude 
      that the term "type 3 diabetes" accurately reflects the fact that AD represents a 
      form of diabetes that selectively involves the brain and has molecular and 
      biochemical features that overlap with both type 1 diabetes mellitus and T2DM.
FAU - de la Monte, Suzanne M
AU  - de la Monte SM
AD  - Department of Pathology, Rhode Island Hospital and the Warren Alpert Medical 
      School at Brown University, Providence, Rhode Island, USA. 
      suzanne_delamonte_md@brown.edu
FAU - Wands, Jack R
AU  - Wands JR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Diabetes Sci Technol
JT  - Journal of diabetes science and technology
JID - 101306166
PMC - PMC2769828
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - central nervous system
OT  - diabetes
OT  - insulin gene expression
OT  - insulin signaling
EDAT- 2009/11/04 06:00
MHDA- 2009/11/04 06:01
PMCR- 2009/11/01
CRDT- 2009/11/04 06:00
PHST- 2009/11/04 06:00 [entrez]
PHST- 2009/11/04 06:00 [pubmed]
PHST- 2009/11/04 06:01 [medline]
PHST- 2009/11/01 00:00 [pmc-release]
AID - dst.2.6.1101 [pii]
AID - 10.1177/193229680800200619 [doi]
PST - ppublish
SO  - J Diabetes Sci Technol. 2008 Nov;2(6):1101-13. doi: 10.1177/193229680800200619.