The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Abstract
CONTEXT: Alzheimer disease (AD) is characterized neuropathologically by the presence of amyloid beta-peptide (Abeta)-containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of Abeta correlates with dementia and whether Abeta alterations precede or follow changes in tau. OBJECTIVES: To determine whether accumulation of Abeta correlates with the earliest signs of cognitive deterioration and to define the relationship between Abeta accumulation and early tau changes. DESIGN, SETTING, AND PATIENTS: Postmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of Abeta variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia. MAIN OUTCOME MEASURES: Levels of total Abeta peptides with intact or truncated amino termini and ending in either amino acid 40 (A(beta)x-40) or 42 (A(beta)x-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score. RESULTS: The levels of both A(beta)x-40 and A(beta)x-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone A(beta)x-42 peptide were higher than those of A(beta)x-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in A(beta)x-40 and A(beta)x-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease. CONCLUSIONS: In this study, levels of total A(beta)x-40 and A(beta)x-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, Abeta was elevated before the occurrence of significant tau pathology. These results support an important role for Abeta in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.
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In the citing paper
“The accumulation of Aβ has been suggested to prompt neurodegeneration, thereby leading to the clinical dementia often witnessed in AD patients [15].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [15]
In the citing paper
“biochemical studies on human AD brain indicated that the soluble pool of Aβ42 correlated best with degree of cognitive loss [108, 118, 130].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [130]
In the citing paper
“Studies have increasingly differentiated between soluble and insoluble pools of Aβ within the brain, where it is the increase in the soluble pool of Aβ42 that tracks best with cognitive decline in AD [108, 118, 130].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [130]
Citations
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Cited by
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Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188
Metadata
- Authors
- Näslund, J.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- Näslund, Jan
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2000-03-22
- Volume
- 283
- Issue
- 12
- Pages
- 1571
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2000706612
- Cited by
- 1,268
- References
- 28
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 32 · 2023: 23 · 2022: 28 · 2021: 32 · 2020: 31 · 2019: 29 · 2018: 34 · 2017: 29 · 2016: 57 · 2015: 56 · 2014: 60 · 2013: 59 · 2012: 65
- FWCI
- 40.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, AG 14996, P01AG002219)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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, cognitive decline, dementia progression, tau protein, amyloid-beta 42, Aβ40, frontal cortex, Clinical Dementia Rating, postmortem brain, neocortex, nursing home residents, amyloid plaques, neurofibrillary tangles
- MeSH terms
- Aged, Aged, 80 and over, Brain, Cognition Disorders, Cross-Sectional Studies, Dementia, Enzyme-Linked Immunosorbent Assay, Female, Frontal Lobe, Humans, Immunoenzyme Techniques, Male, Immunoblotting, Amyloid beta-Peptides, tau Proteins
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