dr. senckenbergische anatomie department of clinical neuroanatomy
DESCRIPTION
Dr. Senckenbergische Anatomie Department of Clinical Neuroanatomy J. W. Goethe-University Frankfurt/Main, Germany. Gender Difference in Alzheimer ’ s Disease Neuropathology EH Corder, E Ghebremedhin, M Taylor, DR Thal, TG Ohm, H Braak. Definition. - PowerPoint PPT PresentationTRANSCRIPT
Gender Difference in Alzheimer’s Disease Neuropathology
EH Corder, E Ghebremedhin, M Taylor, DR Thal, TG Ohm, H Braak
Dr. Senckenbergische AnatomieDepartment of Clinical Neuroanatomy
J. W. Goethe-University Frankfurt/Main, Germany
Alzheimer’s Disease (AD) is a progressive, neurodegenerative disorder, characterized by loss of memory and other cognitive abilities
Definition
Prevalence of AD with Age
Source: The prevalence of AD in Europe: A collaborative study of 1980-1990 findings (EURODEM)
0
5
10
15
20
25
30
35
30-5960-64
65-6970-74
75-7980-84
85-8990+
Population Affected
Pre
vale
nce
of
AD
(%
)
Age (Years)
Risk Factors
• Advanced age
• 4-allele of apolipoprotein E-Gene (ApoE)
• Female gender?
• 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?
Background
Sources of bias in clinical studies
1. Men more often diagnosed with vascular dementia
2. Women live longer from the onset of symptoms until diagnosis
3. Women more often live alone lacking social and instrumental support triggering diagnosis
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?
Neuropathological features of AD
Neurofibrillary tangles (NFT) Amyloid- deposition (A)
Braak and Braak 1991
A-Stage A A-Stage B A-Stage C
Amyloid = A
Neuropathological staging of AD I
NFT-Stages I-II (Entorhinal stages)
NFT-Stages III-IV(Limbic stages)
NFT-Stages V-VI (Neocortical stages)
Braak and Braak 1991Neurofibrillary tangles = NFT
Neuropathological staging of AD II
• 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
Study sample and methods
Proportion attaining NFT Stages I,II, & III
0
0.25
0.5
0.75
1
55 65 75 85 95
Age (years)
Pro
port
ion
Stage I
Stage II
Stage III
NFT Stage for Men & Women
1
2
3
55 65 75 85 95
Age (years)
Mean
NFT
Sta
ge
Men
Women
0
1
2
3
4
50 60 70 80
Age (years)
NF
T S
tag
e
2/3 w 3/3 w 3/4 w
2/3 m 3/3 m 3/4 m
APOE genotype and NT stage
A Stage for Men & Women
0
1
2
55 65 75 85 95
Age (years)
Mean
A
Sta
ge
MenWomen
0
1
2
3
0 1 2 3 4 5 6
NFT stage
SP
sta
ge
45 55 65 75 85 95
SP stage given NFT stage for women
Table 1. SP stage in relation to NFT stage, age, gender and APOE genotype
SP stage at allocortical NFT stages 0 to III Predictor (SE) p-valueIntercept 0.16 (0.04) <0.0001Decade of age*NFT stage 0.11 (0.006) <0.0001Number of 4 alleles 0.30 (0.07) <0.0001APOE 4 gene dose for women aged 60 to 75 0.65 (0.18) 0.0002One or two 2 alleles -0.13 (0.08) 0.11 SP stage for isocortical NFT stages IV to VIPredictor (SE) p-valueIntercept 2.18 (0.25) <0.0001Decade of age from 50 to 99 -0.01 (0.03) 0.77NFT stage 0.15 (0.05) 0.002Number of APOE 4 alleles 0.09 (0.06) 0.15One or two APOE 2 alleles -0.15 (0.05) 0.002
Table 2. APOE genotype and selective mortality
Age (years) 2/- 3/3 3/4 4/4 Total
20-59 11% ( 44) 63% (259) 22% ( 92) 4% (16) 41160-69 13% ( 30) 66% (151) 18% ( 42) 3% ( 7) 23070-79 13% ( 32) 62% (151) 21% ( 50) 4% (10) 243
80-89 14% ( 51) 63% (232) 21% ( 78) 1% ( 5) 36690-105 18% ( 13) 62% ( 45) 20% ( 15) 0% ( 0) 73
Sample 13% (170) 63% (838) 21% (277) 3% (38) 1323
Germany45 15% 60% 28% were 4/- 1031Germany46 16% 61% 25% were 4/- 1557
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
Conclusion
•The pathologic substrate for dementia may differ for men and women
– Older women likely have greater losses of hippocampal pyramidal neurons