Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan
Abstract
To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation…
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It is well established that Aβ42 declines in the CSF of patients with typical late onset AD.
“It is well established that A42 declines in the CSF of patients with typical late onset AD (Motter et al., 1995;Nitsch et al., 1995;Kanai et al., 1998;Andreasen et al., 1999)”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Kanai et al., 1998
CSF Aβ42 levels are typically reduced in dementia of the Alzheimer type (DAT), reflecting its aggregation and deposition as amyloid in the brain.
“Levels of CSF Aβ42 are typically reduced in dementia of the Alzheimer type (DAT),8-11 reflecting its aggregation and deposition as amyloid in the brain,12”
From Decreased cerebrospinal fluid Aβ <sub>42</sub> correlates with brain atrophy in cognitively normal elderly (2009) · cites this paper as [10]
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- Authors
- Kanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., Watanabe, M., Tomidokoro, Y., Shizuka, M., Mizushima, K., Nakamura, T., Igeta, Y., Ikeda, Y., Amari, M., Kawarabayashi, T., Ishiguro, K., Harigaya, Y., Wakabayashi, K., Okamoto, K., Hirai, S., & Shoji, M.
- Affiliations
- Gunma University (JP)
- Tottori University (JP)
- Tohoku University (JP)
- The University of Tokyo (JP)
- Maebashi Red Cross Hospital (JP)
- Tokyo Metropolitan Neurological Hospital (JP)
- Corresponding author
- Shoji, M.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1998-07
- Volume
- 44
- Issue
- 1
- Pages
- 17-26
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2136680662
- Cited by
- 340
- References
- 51
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 9 · 2012: 11
- FWCI
- 14.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, tau protein, Aβ40, amyloid-beta 42, normal aging, disease progression, early diagnosis, sensitivity and specificity
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Peptide Fragments, ROC Curve, Sensitivity and Specificity, Sex Characteristics, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression
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