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Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
Open accessAbstract
Background Disease-modifying treatment strategies for Alzheimer's disease have led to an urgent need for biomarkers to identify the disease at a very early stage. Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI).Methods From a series of 180 consecutive patients with MCI, we assessed 137 who underwent successful lumbar puncture at baseline. Patients at risk of developing dementia were followed clinically for 4-6 years. Additionally, 39 healthy individuals, cognitively stable over 3 years, served as controls. We analysed CSF concentrations of beta amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau181) using Luminex xMAP technology.Findings During follow-up, 57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%) developed other forms of dementia, and 56 (41%) remained cognitively stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and Abeta42 at baseline yielded a sensitivity of 95% and a specificity of 83% for detection of incipient AD in patients with MCI. The relative risk of progression to Alzheimer's disease was substantially increased in patients with MCI who had pathological concentrations of T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio yielded closely similar results (sensitivity 95%, specificity 87%, hazard ratio 19.8).Interpretation Concentrations of T-tau, P-tau181, and Abeta42 in CSF are strongly associated with future development of Alzheimer's disease in patients with MCI.
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“Furthermore, one study shows that some patients with MCI or depression before AD have a more gradual progression to the disease and that they have pathologic Aβ and tau cerebrospinal fluid (CSF) level changes that are not affected by APOE allele status, while the other forms of AD show a strong APOE association (46).”
From Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets (2021) · cites this paper as [46]
In the citing paper
“Increased concentrations of extracellular soluble phosphorylated tau (p-tau) and total tau (t-tau) constitute a reliable index of this intracellular process in mild cognitive impairment due to AD2,3 and AD dementia.2,4”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [3]
In the citing paper
“Majority of studies have reported decreased Aβ1-42, and increased T-tau and P-tau levels in CSF of MCI and AD patients (Hansson et al., 2006; Mattsson et al., 2009; Andreasen et al., 2001, 2003) and our findings are in conformity with those studies.”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Hansson et al., 2006
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“After 2010, the analysis of cerebrospinal fluid (CSF) biomarkers, such as A β 42, total tau (t-tau) and phosphorylated tau (p-tau) were well established and recognized as standard for diagnosis for AD [19].”
Metadata
- Authors
- Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L.
- Affiliations
- Lund University (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Blennow, Kaj
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 5
- Issue
- 3
- Pages
- 228-234
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2161737267
- Cited by
- 1,700
- References
- 43
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 47 · 2023: 43 · 2022: 70 · 2021: 55 · 2020: 114 · 2019: 63 · 2018: 93 · 2017: 60 · 2016: 76 · 2015: 94 · 2014: 109 · 2013: 100 · 2012: 122
- FWCI
- 68.81
- Type
- journal article
- Language
- en
- Open access
- green
- lup.lub.lu.se
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, mild cognitive impairment, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, phosphorylated tau 181, conversion to dementia, early detection of Alzheimer's disease, sensitivity and specificity, risk factors
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Cognition Disorders, Dementia, Female, Follow-Up Studies, Humans, Male, Middle Aged, Peptide Fragments, Phosphorylation, Psychiatric Status Rating Scales, Retrospective Studies, Time Factors, Biomarkers, Chi-Square Distribution, Odds Ratio, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins
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