Difference between revisions of "Genetics of Alzheimer disease"
(Created page with "APOE4 is a major susceptibility gene for Alzheimer’s disease, and leads to accelerated break down in blood brain barrier in the hippocampus and medial temporal lobe (Montagn...") |
|||
| Line 1: | Line 1: | ||
| − | APOE4 is a major susceptibility gene for Alzheimer’s disease, and leads to accelerated break down in blood brain barrier in the hippocampus and medial temporal lobe (Montagne et al, 2020). | + | ''APOE4'' is a major susceptibility gene for Alzheimer’s disease, and leads to accelerated break down in blood brain barrier in the hippocampus and medial temporal lobe (Montagne et al, 2020). |
| − | * The Alzheimer’s Association cautions against routine genetic testing for APOE4 for AD unless they have had genetic counseling because: | + | * The Alzheimer’s Association cautions against routine genetic testing for ''APOE4'' for AD unless they have had genetic counseling because: |
:- The risk is only relative and not deterministic (people with one copy have about three times the risk of developing AD) | :- The risk is only relative and not deterministic (people with one copy have about three times the risk of developing AD) | ||
| Line 10: | Line 10: | ||
| − | Most early onset AD have sporadic, nonfamilial form (or have unidentified polygenic mutations). Only 11% have association with one of 3 known autosomal dominant mutations (PSEN1, PSEN2, APP) (Mendez 2019). | + | Most early onset AD have sporadic, nonfamilial form (or have unidentified polygenic mutations). Only 11% have association with one of 3 known autosomal dominant mutations (''PSEN1, PSEN2, APP'') (Mendez 2019). |
| − | 1) PSEN1 (presenilin 1) mutation | + | 1) ''PSEN1'' (presenilin 1) mutation |
| − | : a. APOE3 Christchurch (R1365) mutation appears protective in PSEN1 carriers – a case report demonstrated despite high brain amyloid levels, the patient had limited tau and symptoms (Arboleda-Velasquez et al, 2019) | + | : a. ''APOE3 Christchurch (R1365)'' mutation appears protective in PSEN1 carriers – a case report demonstrated despite high brain amyloid levels, the patient had limited tau and symptoms (Arboleda-Velasquez et al, 2019) |
| − | 2) PSEN2 | + | 2) ''PSEN2'' |
| − | 3) APP | + | 3) ''APP'' |
Latest revision as of 10:13, 12 June 2021
APOE4 is a major susceptibility gene for Alzheimer’s disease, and leads to accelerated break down in blood brain barrier in the hippocampus and medial temporal lobe (Montagne et al, 2020).
- The Alzheimer’s Association cautions against routine genetic testing for APOE4 for AD unless they have had genetic counseling because:
- - The risk is only relative and not deterministic (people with one copy have about three times the risk of developing AD)
- - There is no treatment for AD
- - Additional issues may arise, such as anxiety about getting dementia, discrimination, or issues obtaining disability or long-term care insurance
Most early onset AD have sporadic, nonfamilial form (or have unidentified polygenic mutations). Only 11% have association with one of 3 known autosomal dominant mutations (PSEN1, PSEN2, APP) (Mendez 2019).
1) PSEN1 (presenilin 1) mutation
- a. APOE3 Christchurch (R1365) mutation appears protective in PSEN1 carriers – a case report demonstrated despite high brain amyloid levels, the patient had limited tau and symptoms (Arboleda-Velasquez et al, 2019)
2) PSEN2
3) APP
References
Alzheimer’s Association Medical and Scientific Advisory Council. Genetic Testing. https://www.alz.org/media/documents/genetic-testing-statement.pdf (2017).
Arboleda-Velasquez, J. F. et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat. Med. 25, 1680–1683 (2019). https://pubmed.ncbi.nlm.nih.gov/31686034/
Mendez, M. F. Early-onset Alzheimer Disease and Its Variants: Contin. Lifelong Learn. Neurol. 25, 34–51 (2019). https://pubmed.ncbi.nlm.nih.gov/30707186/
Montagne, A. et al. APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline. Nature 581, 71–76 (2020). https://pubmed.ncbi.nlm.nih.gov/32376954/
