References Flashcards
AD: Carmona et al, 2018
AD risk gene TREM2 (Chr6p21.1) is an Ig receptor expressed exclusively by microglia that binds bacterial LPS and DNA, involved in modulation of cell proliferation and differentiation, phagocytosis, chemotaxis, and inflammation. Mutations decrease binding. KO mice have neuronal loss
AD: Gong et al, 1995
Tau hyperphosphorylation occurs due to decrease in protein phosphatase A2
AD: Su et al, 2008
Transient tau hyperphosphorylation occurs in hibernating animals due to decreased protein phosphatase A2
AD: Liang et al, 2008
Protein phosphatase A2 expression is decreased in Down syndrome
AD: Katsouri et al, 2016
PGC-1alpha - involved in regulation of metabolic genes, oxidative phosphorylation, and mitochondrial biogenesis - regulates BACE-1 transcription and is decreased in AD patients. Lentivirus gene therapy in mice reduces neuronal loss and amyloid-beta deposition and increases spatial and recognition memory
AD: Hsu et al, 2011
Metformin decreases dementia risk
AD: Imfeld et al, 2012
Metformin increases dementia risk
AD: Craft et al, 2012
Intranasal insulin increases cognition
PD: Breckenridge et al, 2016
Cigarette smoking inversely associated with PD. Rural living, farming, and pesticide exposure all suggested RFs but insufficient evidence
PD: Morales et al, 2012
Glutamate and dopamine interact in the SN and striatum in rats. In SN, glutamate increases dopamine. In striatum, glutamate decreases dopamine uptake, and dopamine decreases glutamate release
PD: Lin et al, 2003
Dopamine modulates glutamatergic responses of striatal medium spiny neurons. Inappropriate activity leads to chorea, or bradykinesia and rigidity
PD: Van Laar et al, 2012
Acetylcholinesterase inhibitor rivastigmine improves cognitive function in PD patients
PD: Braak et al, 2004 (ACh)
PD associated with cholinergic loss in nucleus basalis of Mynert and PPN, which correlates with declining cognitive function
Epilepsy: Walker et al, 2014
Acquired epilepsy involves TLR4 and HMGB1
Epilepsy: Zhao et al, 2017
Monoclonal Abs against HMGB1decrease seizures in all mice except TLR4 KOs
Prion: Bishop et al, 2013
Most cases of vCJD occur in PRNP codon 129 MM homozygotes, but subclinical cases have occurred in MV heterozygotes
Prion: Fernandez-Borges et al, 2017
VV homozygote mice, and to a lesser extent MV heterozygotes, are harder to infect with vCJD and do not develop a florid clinical phenotype
FTD: Wszolek et al, 2006
FTLD-17 mutations can be missense, deletions, or affect the ratio of 3R to 4R tau
FTD: Lashley, 2015
3 main genes involved in FTD are MAPT, GRN, and C9orf72
ALS/FTD: Cruts et al, 2013
C9orf72 mutations may lead to FTD/ALS by leading to translocation of aggregation-prone dipeptide repeat peptides (DPRs)
ALS: Davidson et al, 2016
No association between dipeptide repeat peptides (DPRs), neurodegeneration, and clinical symptoms
HD: Rigamonte et al, 2000
Normal huntingtin protein thought to stabilise neurons, preventing apoptosis from occurring and prolonging cell life
AD: Purro et al, Nature, 2018
Amyloid-beta deposits in patients with iatrogenic CJD were present in the GH they were inoculated with, suggesting the amyloid-beta could have been transmitted too
MSA: Yoshida, 2007
In Caucasians, striatonigral degeneration subtype most common; in SE Asian/Japanese individuals, olivopontocerebellar atrophy subtype relatively more common
PD: Pellicano et al, 2007
Autonomic disturbances, anosmia, depression, and REM sleep behaviour disorder may be prodromal non-motor symptoms of PD
PD: Healy et al, 2008
LRRK2 mutations have an age-related penetrance, from 28% at age 59 to 74% at age 79
PD: Harrison and Dexter, 2013
In neurodegeneration, balance between HDACs and HATs is skewed towards HDACs. Hypomethylation also occurs due to DNMT1s translocation out of the nucleus. Alpha-syn accumulation masks histone H3 by promoting hypoacetylation
