Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles
Abstract INTRODUCTION Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III–VI) stages, which characterize NFTs’ accumulation. METHODS We studied resista...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/dad2.70016 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850041045138538496 |
|---|---|
| author | Yury Loika Stephanie Webster Elena Loiko Alexander M. Kulminski |
| author_facet | Yury Loika Stephanie Webster Elena Loiko Alexander M. Kulminski |
| author_sort | Yury Loika |
| collection | DOAJ |
| description | Abstract INTRODUCTION Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III–VI) stages, which characterize NFTs’ accumulation. METHODS We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP). RESULTS Resistance, characterized by low (0–II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III–VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele. DISCUSSION The identification of factors underlying resistance and resilience against AD‐related pathologies is essential for promoting cognitively healthy aging. Highlights We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD). This study included individuals who were not diagnosed with AD. Braak stages 0–II and III–VI were considered as a measure of resistance and resilience, respectively. Resistance was stronger at ages younger than 85 years in non‐carriers of the apolipoprotein E (APOE) ε4 allele. Resilience increased with age for each APOE allele independently of sex. At age 85 years and older, high resilience (>50%) was observed in women regardless of the APOE allele. |
| format | Article |
| id | doaj-art-6bf7dcac04f1483db5ad17ee75852a24 |
| institution | DOAJ |
| issn | 2352-8729 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| spelling | doaj-art-6bf7dcac04f1483db5ad17ee75852a242025-08-20T02:55:53ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-10-01164n/an/a10.1002/dad2.70016Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE allelesYury Loika0Stephanie Webster1Elena Loiko2Alexander M. Kulminski3Biodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina USABiodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina USABiodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina USABiodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina USAAbstract INTRODUCTION Neurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III–VI) stages, which characterize NFTs’ accumulation. METHODS We studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP). RESULTS Resistance, characterized by low (0–II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III–VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele. DISCUSSION The identification of factors underlying resistance and resilience against AD‐related pathologies is essential for promoting cognitively healthy aging. Highlights We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD). This study included individuals who were not diagnosed with AD. Braak stages 0–II and III–VI were considered as a measure of resistance and resilience, respectively. Resistance was stronger at ages younger than 85 years in non‐carriers of the apolipoprotein E (APOE) ε4 allele. Resilience increased with age for each APOE allele independently of sex. At age 85 years and older, high resilience (>50%) was observed in women regardless of the APOE allele.https://doi.org/10.1002/dad2.70016agingtau pathologyAlzheimer's diseaseAPOE alleleBraak stagescognitive health |
| spellingShingle | Yury Loika Stephanie Webster Elena Loiko Alexander M. Kulminski Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring aging tau pathology Alzheimer's disease APOE allele Braak stages cognitive health |
| title | Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles |
| title_full | Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles |
| title_fullStr | Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles |
| title_full_unstemmed | Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles |
| title_short | Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles |
| title_sort | resistance and resilience to tau pathology in alzheimer s disease effects of age sex and apoe alleles |
| topic | aging tau pathology Alzheimer's disease APOE allele Braak stages cognitive health |
| url | https://doi.org/10.1002/dad2.70016 |
| work_keys_str_mv | AT yuryloika resistanceandresiliencetotaupathologyinalzheimersdiseaseeffectsofagesexandapoealleles AT stephaniewebster resistanceandresiliencetotaupathologyinalzheimersdiseaseeffectsofagesexandapoealleles AT elenaloiko resistanceandresiliencetotaupathologyinalzheimersdiseaseeffectsofagesexandapoealleles AT alexandermkulminski resistanceandresiliencetotaupathologyinalzheimersdiseaseeffectsofagesexandapoealleles |