Dementia 5

Question 1

What is the main genetic risk factor for Alzheimers?

What is a genetic protective factor for Alzheimers?

Answer 1

Increased Risk (not causation) = ApoE (Apoliproprotein E), epsilon 4 allele.

Protective = ApoE (Apoliproprotein E), epsilon 2 allele

Question 2

What are the 10 main risk factors for Alzheimer’s?

Answer 2

H(2)OAL C(3)F(2)

1. Homocysteine (chronic elevation)
2. HLD
3. Old age
4. APO E 4
5. Lower Education
6. Chronic periodontitits
7. Chronic Anticholinergic exposure
8. CV risk factors
9. Family hx
10. Female

Question 3

What are 3 protective factors for Alzheimer’s?

Answer 3

1. Exercise
2. High n-3 fatty acids
3. ApoE epsilon 2 allele

Question 4

Alzheimers disease has a progressive course…how many years after dx to death?

Answer 4

10 years.

Question 5

Which autosomal dominant genetic mutation causes early onset Alzheimers disease?

Answer 5

Presenilin 1 gene

AND

Presenilin 2 gene

AND

APP (Amyloid Precursor Protein) gene

Question 6

What are the 4 pathological/histological findings in Alzheimers?

Answer 6

1. Senile “neuritic” Plaques (extracellular glial cells + Amyloid Beta-42 ~insoluble form)
2. Neurofibrillary tangles (intracellular microtubular proteins of ubiquitin and phosphorylated Tau)
3. Early neuronal loss (think Hippocampal CA1 cells)
4. Amyloid angiopathy (Amyloid B arterial plaques)

Question 7

Though the use of “biomarkers” are not recommended for diagnosis of Alzheimers…What are the 6 known biomarkers?

Answer 7

Biomarker of amyloid deposition:

1. Low CSF Amyloid Beta-42
2. PET –> Amyloid deposits seen

Biomarker of neuronal injury:

4. Increased Tau in CSF
5. PET –> decreased glucose uptake in temporal and parietal lobes.
6. MRI –> Atrophy in temporal and parietal lobes.

Question 8

Early onset Alzheimers is before what age? What percentage is through autosomal dominant Familial Disease and what percentage is “sporadic” like the late onset disease?

Answer 8

65 years old.

Of those with early onset Alzheimers, 50% have autosomal dominant early onset familial disease (eFAD) and 50% is sporadic.

Question 9

What are the three gene mutations that can independently cause the autosomal dominant form of Early Onset Alzheimers Disease? What chromosome are they on?

Answer 9

Missense mutation of:

1. Presenilin 1 (chromosome 14)
2. Presenilin 2 (chromosome 1)
3. Amyloid Precursor Protein (APP, on chromosome 21)

Question 10

How does Presenilin 1 and Presenilin 2 missense mutations cause early onset Alzheimers?

Answer 10

Presenilin 1 and 2 code for proteases that cleave Amyloid Precursor Protein…abnormal cleavage causes increase in Amyloid B-42, the insoluble form, which aggregates extracellularly, in Senile plagues. AB-42 also encourages influx of Ca2+ which leads to neuronal death.