Gender Difference in Alzheimers Disease Neuropathology EH Corder, E Ghebremedhin, M Taylor, DR Thal,

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Gender Difference in Alzheimers Disease
Neuropathology EH Corder, E Ghebremedhin, M
Taylor, DR Thal, TG Ohm, H Braak
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Definition
Alzheimers Disease (AD) is a progressive,
neurodegenerative disorder, characterized by loss
of memory and other cognitive abilities
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Prevalence of AD with Age
Source The prevalence of AD in Europe A
collaborative study of 1980-1990 findings
(EURODEM)
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Risk Factors

• Advanced age
• ?4-allele of apolipoprotein E-Gene (ApoE)
• Female gender?

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Background

• Prevalence About 2-3 times as many women as men
  have AD-- Women live longer.
• Incidence Are women at higher risk at each age?
• Does gender make a difference in the pathogenesis
  of AD?

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Sources of bias in clinical studies

• Men more often diagnosed with vascular dementia
• Women live longer from the onset of symptoms
  until diagnosis
• 3. Women more often live alone lacking social and
  instrumental support triggering diagnosis

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Objective

• To compare AD changes for men and women at each
  age.
• Are women more susceptible?
• Do men and women have the same
• pathologic substrate for AD dementia?

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Neuropathological features of AD
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Neuropathological staging of AD I
Braak and Braak 1991
Amyloid ? A?
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Neuropathological staging of AD II
Braak and Braak 1991
Neurofibrillary tangles NFT
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Study sample and methods

• 5615 (3165 men and 2450 women) consecutive
  autopsy cases aged 20 105 years
• All brains were assessed for NFT- and A?-
  pathology
• Linear regression analysis was used to predict
  stage by age and gender

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Proportion attaining NFT Stages I,II, III
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NFT Stage for Men Women

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APOE genotype and NT stage
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A? Stage for Men Women
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SP stage given NFT stage for women
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Table 1. SP stage in relation to NFT stage, age,
gender and APOE genotype SP stage at
allocortical NFT stages 0 to III Predictor
b (SE) p-value Intercept 0.16
(0.04) lt0.0001 Decade of ageNFT stage 0.11
(0.006) lt0.0001 Number of e4 alleles 0.30
(0.07) lt0.0001 APOE e4 gene dose for women aged
60 to 75 0.65 (0.18) 0.0002 One or two e2
alleles -0.13 (0.08) 0.11   SP stage for
isocortical NFT stages IV to VI Predictor b
(SE) p-value Intercept 2.18
(0.25) lt0.0001 Decade of age from 50 to
99 -0.01 (0.03) 0.77 NFT stage 0.15
(0.05) 0.002 Number of APOE e4 alleles 0.09
(0.06) 0.15 One or two APOE e2 alleles -0.15
(0.05) 0.002
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Table 2. APOE genotype and selective
mortality Age (years) e2/- e3/3 e3/4 e4/4
Total 20-59 11 ( 44) 63 (259) 22 (
92) 4 (16) 411 60-69 13 ( 30) 66 (151) 18 (
42) 3 ( 7) 230 70-79 13 ( 32) 62 (151) 21 (
50) 4 (10) 243 80-89 14 ( 51) 63 (232) 21
( 78) 1 ( 5) 366 90-105 18 ( 13) 62 (
45) 20 ( 15) 0 ( 0) 73 Sample 13
(170) 63 (838) 21 (277) 3 (38) 1323 Germany45
15 60 28 were e4/- 1031 Germany46 16 61 25
were e4/- 1557
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Summary

• Women have a 3-year acceleration in tangle
  neuropathology associated with APOE4
• APOE4 women have a large jump in senile plaque
  distribution in late middle age

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Conclusion

• The pathologic substrate for dementia may differ
  for men and women
• Older women likely have greater losses of
  hippocampal pyramidal neurons