Cited by 1,268Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline

Näslund, Jan·2000·JAMA

DOI 10.1001/jama.283.12.1571

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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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Background
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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
DOI: 10.1001/jama.283.12.1571
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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Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline

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