PMID- 31081340
OWN - NLM
STAT- MEDLINE
DCOM- 20200513
LR  - 20240414
IS  - 1759-0914 (Electronic)
IS  - 1759-0914 (Linking)
VI  - 11
DP  - 2019 Jan-Dec
TI  - Altered Brain Expression of Insulin and Insulin-Like Growth Factors in 
      Frontotemporal Lobar Degeneration: Another Degenerative Disease Linked to 
      Dysregulation of Insulin Metabolic Pathways.
PG  - 1759091419839515
LID - 10.1177/1759091419839515 [doi]
LID - 1759091419839515
AB  - BACKGROUND: Frontotemporal lobar degeneration (FTLD) is the third most common 
      dementing neurodegenerative disease with nearly 80% having no known etiology. 
      OBJECTIVE: Growing evidence that neurodegeneration can be linked to dysregulated 
      metabolism prompted us to measure a panel of trophic factors, receptors, and 
      molecules that modulate brain metabolic function in FTLD. METHODS: Postmortem 
      frontal (Brodmann's area [BA]8/9 and BA24) and temporal (BA38) lobe homogenates 
      were used to measure immunoreactivity to Tau, phosphorylated tau (pTau), 
      ubiquitin, 4-hydroxynonenal (HNE), transforming growth factor-beta 1 (TGF-beta1) and 
      its receptor (TGF-beta1R), brain-derived neurotrophic factor (BDNF), nerve growth 
      factor, neurotrophin-3, neurotrophin-4, tropomyosin receptor kinase, and insulin 
      and insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) 
      and their receptors by direct-binding enzyme-linked immunosorbent assay. RESULTS: 
      FTLD brains had significantly elevated pTau, ubiquitin, TGF-beta1, and HNE 
      immunoreactivity relative to control. In addition, BDNF and neurotrophin-4 were 
      respectively reduced in BA8/9 and BA38, while neurotrophin-3 and nerve growth 
      factor were upregulated in BA38, and tropomyosin receptor kinase was elevated in 
      BA24. Lastly, insulin and insulin receptor expressions were elevated in the 
      frontal lobe, IGF-1 was increased in BA24, IGF-1R was upregulated in all three 
      brain regions, and IGF-2 receptor was reduced in BA24 and BA38. CONCLUSIONS: 
      Aberrantly increased levels of pTau, ubiquitin, HNE, and TGF-beta1, marking 
      neurodegeneration, oxidative stress, and neuroinflammation, overlap with altered 
      expression of insulin/IGF signaling ligand and receptors in frontal and temporal 
      lobe regions targeted by FTLD. Dysregulation of insulin-IGF signaling networks 
      could account for brain hypometabolism and several characteristic neuropathologic 
      features that characterize FTLD but overlap with Alzheimer's disease, Parkinson's 
      disease, and Dementia with Lewy Body Disease.
FAU - Liou, Connie J
AU  - Liou CJ
AD  - 1 Warren Alpert Medical School of Brown University, Providence, RI, USA.
FAU - Tong, Ming
AU  - Tong M
AD  - 1 Warren Alpert Medical School of Brown University, Providence, RI, USA.
AD  - 2 Division of Neuropathology, Departments of Pathology, Medicine, Neurology, and 
      Neurosurgery, Rhode Island Hospital, Providence, RI, USA.
AD  - 3 Department of Pathology and Laboratory Medicine, the Providence VA Medical 
      Center, Providence, RI, USA.
FAU - Vonsattel, Jean P
AU  - Vonsattel JP
AD  - 4 New York Brain Bank, Taub Institute, Columbia University, New York, NY, USA.
FAU - de la Monte, Suzanne M
AU  - de la Monte SM
AD  - 1 Warren Alpert Medical School of Brown University, Providence, RI, USA.
AD  - 2 Division of Neuropathology, Departments of Pathology, Medicine, Neurology, and 
      Neurosurgery, Rhode Island Hospital, Providence, RI, USA.
AD  - 3 Department of Pathology and Laboratory Medicine, the Providence VA Medical 
      Center, Providence, RI, USA.
LA  - eng
GR  - R01 AA012908/AA/NIAAA NIH HHS/United States
GR  - R21 NS096525/NS/NINDS NIH HHS/United States
GR  - R37 AA011431/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - ASN Neuro
JT  - ASN neuro
JID - 101507115
RN  - 0 (Insulin)
RN  - 0 (Somatomedins)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain/*metabolism
MH  - Female
MH  - Frontotemporal Lobar Degeneration/*metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Male
MH  - Somatomedins/*metabolism
PMC - PMC6535914
OTO - NOTNLM
OT  - neurodegenerative diseases
OT  - neurodevelopmental disorders
OT  - neuropathology
EDAT- 2019/05/14 06:00
MHDA- 2020/05/14 06:00
PMCR- 2019/05/12
CRDT- 2019/05/14 06:00
PHST- 2019/05/14 06:00 [entrez]
PHST- 2019/05/14 06:00 [pubmed]
PHST- 2020/05/14 06:00 [medline]
PHST- 2019/05/12 00:00 [pmc-release]
AID - 10.1177_1759091419839515 [pii]
AID - 10.1177/1759091419839515 [doi]
PST - ppublish
SO  - ASN Neuro. 2019 Jan-Dec;11:1759091419839515. doi: 10.1177/1759091419839515.