Distinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Open accessAbstract
OBJECTIVE: To determine whether beta-amyloid (Abeta) peptides segregated into distinct biochemical compartments would differentially correlate with clinical severity of Alzheimer disease (AD). DESIGN: Clinicopathologic correlation study. PARTICIPANTS: Twenty-seven patients from a longitudinal study of AD and 13 age- and sex-matched controls without a known history of cognitive impairment or dementia were included in this study. INTERVENTIONS: Temporal and cingulate neocortex were processed using a 4-step extraction, yielding biochemical fractions that are hypothesized to be enriched with proteins from distinct anatomical compartments: TRIS (extracellular soluble), Triton (intracellular soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid (extracellular insoluble). Levels of Abeta(40) and Abeta(42) were quantified in each biochemical compartment by enzyme-linked immunosorbent assay. RESULTS: The Abeta(42) level in all biochemical compartments was significantly elevated in patients with AD vs controls (P < .01). The Abeta(40) levels in the TRIS and formic acid fractions were elevated in patients with AD (temporal, P < .01; cingulate, P = .03); however, Triton and SDS Abeta(40) levels were similar in patients with AD and in controls. Functional impairment proximal to death correlated with Triton Abeta(42) (r = 0.48, P = .02) and SDS Abeta(42) (r = 0.41, P = .04) in the temporal cortex. Faster cognitive decline was associated with elevated temporal SDS Abeta(42) levels (P < .001), whereas slower decline was associated with elevated cingulate formic acid Abeta(42) and SDS Abeta(42) levels (P = .02 and P = .01, respectively). CONCLUSION: Intracellular and membrane-associated Abeta, especially Abeta(42) in the temporal neocortex, may be more closely related to AD symptoms than other measured Abeta species.
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A recent study indicated that cognitive decline in AD tracked best with the membranous pool of Aβ42 in brain tissue from human AD; it was concluded that this membrane-associated Aβ42 was cell associated and reflected intraneuronal Aβ42.
“a recent study indicated that cognitive decline in AD tracked best with the membranous pool of Aβ42 in brain tissue from human AD [180]; it was concluded that this membrane-associated Aβ42 was cell associated and reflected intraneuronal Aβ42.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [180]
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- Authors
- Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y.
- Affiliations
- Columbia University Irving Medical Center (US)
- Harvard University (US)
- Johns Hopkins University (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-07-01
- Volume
- 65
- Issue
- 7
- Pages
- 906-12
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2586606
- OpenAlex
- W2002793086
- Cited by
- 104
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 1 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ag007370-30)
- National Institute on Aging (R01-AG07370, R01-AG007370, P50 AG05134, P50AG005134)
- National Institute of Mental Health (T32MH020004)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, Alzheimer's disease, amyloid-beta 42, Aβ40, biochemical fractionation, extracellular amyloid, temporal cortex, cingulate cortex, cognitive decline, clinicopathological correlation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Brief Psychiatric Rating Scale, Amyloid beta-Peptides, Plaque, Amyloid
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