Target intelligence / Profile preview

Alzheimer's disease biomarkers (AD biomarkers)

Target
AD biomarkers
Molecular classification
Protein, Peptide, Enzyme, Lipid, Metabolite
01

Overview

Alzheimer's disease biomarkers are a collective set of biological indicators used to identify the presence of Alzheimer's pathology, including Amyloid-beta (Aβ) and Tau proteins (Jack et al., 2018, Lancet Neurology). These biomarkers, such as the Aβ42/40 ratio and various phosphorylated tau species (e.g., p-tau217), are essential for diagnosing the disease in both clinical and research settings (Hansson et al., 2023, Nature Medicine). While the term refers to a category rather than a single receptor, the individual components like Aβ and Tau serve as the primary therapeutic targets for recently approved disease-modifying treatments (Cummings et al., 2024, Alzheimer's & Dementia). For instance, monoclonal antibodies like Lecanemab target Aβ protofibrils to reduce plaque burden and slow cognitive decline (van Dyck et al., 2023, NEJM). Additionally, biomarkers like Neurofilament light chain (NfL) provide insights into general neurodegeneration and axonal damage (Khalil et al., 2018, Nature Reviews Neurology). Monitoring these biomarkers is critical for patient selection and assessing the safety and efficacy of anti-amyloid and anti-tau therapies.

Other names
AD biomarkersDementia biomarkersCerebrospinal fluid biomarkersNeurodegenerative biomarkersATN framework indicators
02

Mechanism of action

Therapeutic strategies targeting these biomarkers primarily involve monoclonal antibodies that bind to Amyloid-beta aggregates to promote their clearance via microglial-mediated phagocytosis (Sevigny et al., 2016, Nature). Other mechanisms include the inhibition of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) to reduce Aβ production, although many such trials have faced challenges (Knopman, 2019, Alzheimer's & Dementia). Experimental tau-targeted therapies aim to inhibit tau aggregation or promote the clearance of hyperphosphorylated tau species to prevent the spread of neurofibrillary tangles (Mullard, 2021, Nature Reviews Drug Discovery).

03

Biological functions

Protein foldingMicrotubule stabilizationAxonal integrityProteolysisNeuroinflammation
04

Disease associations

Neurodegenerative diseaseAlzheimer's diseaseDementiaCognitive impairment
05

Safety considerations

Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H) (Sperling et al., 2011, Alzheimer's & Dementia)Infusion-related reactionsBrain volume loss (pseudoatrophy)Potential for off-target neuroinflammationCerebral microhemorrhages (FDA Leqembi Prescribing Information, 2023)
06

Interacting drugs

Aducanumab

6 more in the full profile.

07

Biomarkers

Amyloid-beta 42/40 ratioPhosphorylated tau (p-tau181, p-tau217, p-tau231)Total tau (t-tau)Neurofilament light chain (NfL)Glial fibrillary acidic protein (GFAP)Triggering receptor expressed on myeloid cells 2 (TREM2)

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