References

Question 1

AD: Carmona et al, 2018

Answer 1

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

Question 2

AD: Gong et al, 1995

Answer 2

Tau hyperphosphorylation occurs due to decrease in protein phosphatase A2

Question 3

AD: Su et al, 2008

Answer 3

Transient tau hyperphosphorylation occurs in hibernating animals due to decreased protein phosphatase A2

Question 4

AD: Liang et al, 2008

Answer 4

Protein phosphatase A2 expression is decreased in Down syndrome

Question 5

AD: Katsouri et al, 2016

Answer 5

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

Question 6

AD: Hsu et al, 2011

Answer 6

Metformin decreases dementia risk

Question 7

AD: Imfeld et al, 2012

Answer 7

Metformin increases dementia risk

Question 8

AD: Craft et al, 2012

Answer 8

Intranasal insulin increases cognition

Question 9

PD: Breckenridge et al, 2016

Answer 9

Cigarette smoking inversely associated with PD. Rural living, farming, and pesticide exposure all suggested RFs but insufficient evidence

Question 10

PD: Morales et al, 2012

Answer 10

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

Question 11

PD: Lin et al, 2003

Answer 11

Dopamine modulates glutamatergic responses of striatal medium spiny neurons. Inappropriate activity leads to chorea, or bradykinesia and rigidity

Question 12

PD: Van Laar et al, 2012

Answer 12

Acetylcholinesterase inhibitor rivastigmine improves cognitive function in PD patients

Question 13

PD: Braak et al, 2004 (ACh)

Answer 13

PD associated with cholinergic loss in nucleus basalis of Mynert and PPN, which correlates with declining cognitive function

Question 14

Epilepsy: Walker et al, 2014

Answer 14

Acquired epilepsy involves TLR4 and HMGB1

Question 15

Epilepsy: Zhao et al, 2017

Answer 15

Monoclonal Abs against HMGB1decrease seizures in all mice except TLR4 KOs

Question 16

Prion: Bishop et al, 2013

Answer 16

Most cases of vCJD occur in PRNP codon 129 MM homozygotes, but subclinical cases have occurred in MV heterozygotes

Question 17

Prion: Fernandez-Borges et al, 2017

Answer 17

VV homozygote mice, and to a lesser extent MV heterozygotes, are harder to infect with vCJD and do not develop a florid clinical phenotype

Question 18

FTD: Wszolek et al, 2006

Answer 18

FTLD-17 mutations can be missense, deletions, or affect the ratio of 3R to 4R tau

Question 19

FTD: Lashley, 2015

Answer 19

3 main genes involved in FTD are MAPT, GRN, and C9orf72

Question 20

ALS/FTD: Cruts et al, 2013

Answer 20

C9orf72 mutations may lead to FTD/ALS by leading to translocation of aggregation-prone dipeptide repeat peptides (DPRs)

Question 21

ALS: Davidson et al, 2016

Answer 21

No association between dipeptide repeat peptides (DPRs), neurodegeneration, and clinical symptoms

Question 22

HD: Rigamonte et al, 2000

Answer 22

Normal huntingtin protein thought to stabilise neurons, preventing apoptosis from occurring and prolonging cell life

Question 23

AD: Purro et al, Nature, 2018

Answer 23

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

Question 24

MSA: Yoshida, 2007

Answer 24

In Caucasians, striatonigral degeneration subtype most common; in SE Asian/Japanese individuals, olivopontocerebellar atrophy subtype relatively more common

Question 25

PD: Pellicano et al, 2007

Answer 25

Autonomic disturbances, anosmia, depression, and REM sleep behaviour disorder may be prodromal non-motor symptoms of PD

Question 26

PD: Healy et al, 2008

Answer 26

LRRK2 mutations have an age-related penetrance, from 28% at age 59 to 74% at age 79

Question 27

PD: Harrison and Dexter, 2013

Answer 27

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