PMID- 34842187
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 85
IP  - 2
DP  - 2022
TI  - A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with 
      Alzheimer's Disease.
PG  - 485-501
LID - 10.3233/JAD-210612 [doi]
AB  - Dementias, including the type associated with Alzheimer's disease (AD), are on 
      the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most 
      prevalent chronic diseases globally. Although mechanisms and treatments are 
      well-established for T2DM, there remains much to be discovered. Recent research 
      efforts have further investigated factors involved in the etiology of AD. 
      Previously perceived to be unrelated diseases, commonalities between T2DM and AD 
      have more recently been observed. As a result, AD has been labeled as "type 3 
      diabetes". In this review, we detail the shared processes that contribute to 
      these two diseases. Insulin resistance, the main component of the pathogenesis of 
      T2DM, is also present in AD, causing impaired brain glucose metabolism, 
      neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors 
      and components of the insulin signaling pathway, including protein kinase B, 
      glycogen synthase kinase 3beta, and mammalian target of rapamycin are reported in 
      both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, 
      mitochondrial dysfunction, advanced glycation end products, and amyloid 
      deposition. The impact that changes in neurovascular structure and genetics have 
      on the development of these conditions is also being examined. With the discovery 
      of factors contributing to AD, innovative treatment approaches are being 
      explored. Investigators are evaluating the efficacy of various T2DM medications 
      for possible use in AD, including but not limited to glucagon-like peptide-1 
      receptor agonists and peroxisome proliferator-activated receptor-gamma agonists. 
      Furthermore, there are 136 active trials involving 121 therapeutic agents 
      targeting novel AD biomarkers. With these efforts, we are one step closer to 
      alleviating the ravaging impact of AD on our communities.
FAU - Lynn, Jessica
AU  - Lynn J
AD  - Massachusetts College of Pharmacy & Health Sciences (MCPHS University)/Takeda 
      Pharmaceuticals Biopharmaceutical Industry Fellowship Program, Boston, MA, USA.
FAU - Park, Mingi
AU  - Park M
AD  - Massachusetts College of Pharmacy & Health Sciences (MCPHS University)/Takeda 
      Pharmaceuticals Biopharmaceutical Industry Fellowship Program, Boston, MA, USA.
FAU - Ogunwale, Christiana
AU  - Ogunwale C
AD  - Walgreen Company, Houston, TX, USA.
FAU - Acquaah-Mensah, George K
AU  - Acquaah-Mensah GK
AD  - Massachusetts College of Pharmacy & Health Sciences (MCPHS University)/Takeda 
      Pharmaceuticals Biopharmaceutical Industry Fellowship Program, Boston, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Biomarkers)
RN  - 0 (Glycation End Products, Advanced)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Alzheimer Disease/*chemically induced/*metabolism/therapy
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Brain Chemistry/*physiology
MH  - Cognitive Dysfunction/metabolism
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Glucose/*metabolism
MH  - Glycation End Products, Advanced/metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Insulin Resistance
MH  - Oxidative Stress/physiology
MH  - Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid
OT  - blood-brain barrier
OT  - glucagon-like peptide 1
OT  - insulin resistance
OT  - microbiota
OT  - mitochondria
OT  - oxidative stress
OT  - therapeutics
OT  - type 2 diabetes mellitus
EDAT- 2021/11/30 06:00
MHDA- 2022/03/01 06:00
CRDT- 2021/11/29 09:00
PHST- 2021/11/30 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2021/11/29 09:00 [entrez]
AID - JAD210612 [pii]
AID - 10.3233/JAD-210612 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2022;85(2):485-501. doi: 10.3233/JAD-210612.