Biomarkers for Alzheimer's disease: current status and prospects for the future

Blennow, K.; Zetterberg, H.

doi:10.1111/joim.12816

Cited by 1,000Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

Biomarkers for Alzheimer's disease: current status and prospects for the future

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Blennow, K., Zetterberg, H.·2018·Journal of Internal Medicine

DOI 10.1111/joim.12816

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Abstract

Accumulating data from the clinical research support that the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid‐β (Aβ42), total tau (T‐tau), and phosphorylated tau (P‐tau) reflect key elements of AD pathophysiology. Importantly, a large number of clinical studies very consistently show that these biomarkers contribute with diagnostically relevant information, also in the early disease stages. Recent technical developments have made it possible to measure these biomarkers using fully automated assays with high precision and stability. Standardization efforts have given certified reference materials for CSF Aβ42, with the aim to harmonize results between assay formats that would allow for uniform global reference limits and cut‐off values. These encouraging developments have led to that the core AD CSF biomarkers have a central position in the novel diagnostic criteria for the disease and in the recent National Institute on Aging and Alzheimer's Association biological definition of AD. Taken together, this progress will likely serve as the basis for a more general introduction of these diagnostic tests in clinical routine practice. However, the heterogeneity of pathology in late‐onset AD calls for an expansion of the AD CSF biomarker toolbox with additional biomarkers reflecting additional aspects of AD pathophysiology. One promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration. Further, recent studies bring hope for easily accessible and cost‐effective screening tools in the early diagnostic evaluation of patients with cognitive problems (and suspected AD) in primary care. In this respect, technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis (the Aβ42/40 or APP669‐711/Aβ42 ratios) and neurodegeneration (tau and neurofilament light proteins) in plasma samples, but future studies are warranted to validate these promising results further.

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Many CSF biomarkers (like Aβ, P-tau, NfL, GFAP) also show promising applications in blood, with advancements in highly sensitive analytical platforms and detection techniques enhancing diagnostic precision and reliability.
“Many CSF biomarkers (like Aβ, P-tau, NfL, GFAP) also show promising applications in blood, with advancements in highly sensitive analytical platforms and detection techniques enhancing diagnostic precision and reliability.368,388,389”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [389]
The “Blood biomarkers for AD” section says ultrasensitive immunoassays and mass spectrometry offer hope for blood biomarkers, and the sections on plasma Aβ and neurofilament light describe promising results. But the paper does not establish promising blood applications for every biomarker listed: “Tau protein in plasma” says plasma tau was not yet diagnostically useful and blood P-tau required further validation, while the retrieved passages do not discuss blood GFAP. The claim also overstates the paper’s cautious assessment of diagnostic reliability. (LLM, conf=0.88)
Experimental — accuracy not yet measured
A CSF biomarker profile defined by reduced levels of Aβ42 in conjunction with elevated t-tau and p-tau provides a robust biochemical signature for detecting AD pathology and distinguishing it from other neurodegenerative disorders.
“A characteristic biomarker profile, defined by reduced levels of Aβ42 in conjunction with elevated t-tau and p-tau, provides a robust biochemical signature for detecting AD pathology and distinguishing it from other neurodegenerative disorders72,73.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [72]
An ELISA assay called INNOTEST has been used for two decades for quantification of t-tau, p-tau and Aβ42 in CSF, giving a unique 'Alzheimer's CSF profile' where an increased level of t-tau and p-tau is observed with decreased Aβ42 level.
“An ELISA assay called as INNOTEST has been used for two decades for quantification of t-tau, p-tau and Aβ42 in CSF which gives a unique ‘Alzheimer’s CSF profile’ where an increased level of t-tau and p-tau is observed with decreased Aβ42 level [45, 46].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [45]
Familial Alzheimer's disease is inherited from parents and accounts for <1% of the AD burden.
“Familial Alzheimer's disease is inherited from parents and it currently accounts for < 1% of the AD burden [45].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [45]

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Novel plasma biomarker surrogating cerebral amyloid deposition
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Authors: Blennow, K., & Zetterberg, H.
Affiliations: University of Gothenburg (SE)
Corresponding author: Blennow, K.
ORCID: Blennow, K.
Zetterberg, H.
Venue: Journal of Internal Medicine
Publisher: Wiley
Published: 2018-08-19
Volume: 284
Issue: 6
Pages: 643-663
ISSN: 0954-6820 (ISSN-L)
1365-2796
DOI: 10.1111/joim.12816
OpenAlex: W2884982789
Cited by: 1,000
References: 160
Citations by year: 2026: 102 · 2025: 158 · 2024: 158 · 2023: 162 · 2022: 148 · 2021: 144 · 2020: 89 · 2019: 32 · 2018: 6
FWCI: 10.52
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Royal Swedish Academy of Sciences
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords: Alzheimer's disease, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, phosphorylated tau, neurogranin, neurofilament light chain, early diagnosis, diagnostic criteria, certified reference materials, cerebral amyloidosis, neurodegeneration, plasma biomarkers, ultrasensitive immunoassay, mass spectrometry, primary care screening, cognitive decline
MeSH terms: Alzheimer Disease, Forecasting, Humans, Biomarkers, Amyloid beta-Peptides, tau Proteins, Early Diagnosis

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Biomarkers for Alzheimer's disease: current status and prospects for the future

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