Dissociation of Neuropathologic Findings and Cognition: Case Report of an Apolipoprotein E ε2/ε2 Genotype
Abstract
Background The apolipoprotein E (APOE) epsilon2 allele has been suggested as having a protective effect and delaying the age at onset of Alzheimer disease.Objective To describe a dissociation between neuropathologic findings with normal cognition in a woman with severe Alzheimer disease with the APOE epsilon2/epsilon2 genotype.Design Case report from a community-based prospective study of persons 90 years or older (The 90+ Study).Participant A 92-year-old woman without dementia with the APOE epsilon2/epsilon2 genotype who lived independently without significant cognitive or functional loss and was a participant in The 90+ Study. She died in December 2004, and postmortem examination of her brain was performed.Intervention Neurologic examination and a battery of neuropsychological tests were performed 6 months and 1 month before death. Neuropathologic examination included Braak and Braak staging for senile plaques and neurofibrillary tangles.Results Neuropathologic examination of the brain revealed advanced senile plaque and neurofibrillary tangle disease consistent with a high likelihood of Alzheimer disease. At clinical evaluation, the participant demonstrated no dementia and only mild cognitive deficits.Conclusions The APOE genotype may have contributed to maintenance of cognition despite advanced neuropathologic findings of Alzheimer disease. This case suggests that the APOE epsilon2 isoform may have a protective effect against cognitive decline in Alzheimer disease that may be independent from senile plaques and neurofibrillary tangles.
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APOE2-induced deposition of diffuse plaques is novel in a mouse model and consistent with previous work by Dr. C. Kawas and co-workers.
“This APOE2induced deposition of diffuse plaques is novel in a mouse model and consistent with the previous work by Dr. C. Kawas and co-workers (54,55) who report that increased diffuse plaques are associated with APOE2 in cognitively normal subjects compared with compact plaques in APOE4 AD patients from the oldest of the old study.”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [55]
The single case report outlier, a Braak neuropathologic stage VI case without full-blown dementia, had some degree of cognitive impairment within expectations for late preclinical Alzheimer disease.
“Even the single case report “outlier,” a Braak neuropathologic stage VI case without full-blown dementia, had some degree of cognitive impairment within expectations for late preclinical AD (306).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [306]
Some cases classified as 'high level' of AD neuropathological changes may show subtle or undetectable cognitive impairment.
“Some cases classified as “high level” of AD neuropathological changes may show subtle or undetectable cognitive impairment, yet all cases with quantifiably “end stage” neocortical NFT pathology show cognitive impairment (Dickson et al., 1995; Berlau et al., 2007; Nelson et al., 2009a, 2012; Abner et al., 2011; Santacruz et al., 2011; Jicha et al., 2012).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Berlau et al., 2007
All cases with quantifiably 'end stage' neocortical NFT pathology show cognitive impairment.
“Some cases classified as “high level” of AD neuropathological changes may show subtle or undetectable cognitive impairment, yet all cases with quantifiably “end stage” neocortical NFT pathology show cognitive impairment (Dickson et al., 1995; Berlau et al., 2007; Nelson et al., 2009a, 2012; Abner et al., 2011; Santacruz et al., 2011; Jicha et al., 2012).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Berlau et al., 2007
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References 21
- Authors
- Berlau, D. J., Kahle-Wrobleski, K., Head, E., Goodus, M., Kim, R., & Kawas, C.
- Affiliations
- University of California, Irvine (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2007-08-01
- Volume
- 64
- Issue
- 8
- Pages
- 1193
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W1542516994
- Cited by
- 0
- References
- 21
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- Funders
- National Institute on Aging (R01 AG21055, R01AG021055)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- cognitive impairment, dissociation, neuropathology, dementia
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