LITERATURE UPDATE
An overview of the genes and biomarkers in Alzheimer’s disease Krishnamurthy HK, Jayaraman V, Krishna K et al. Ageing Res Rev. 2025 Feb; 104: 102599. doi: 10.1016/
j.arr.2024.102599.
Alzheimer’s disease (AD) is the most common type of dementia and neurodegenerative disease characterised by neurofibrillary tangles (NFTs) and amyloid plaque. Familial AD is caused by mutations in the APP, PSEN1, and PSEN2 genes and these mutations result in the early onset of the disease. Sporadic AD usually affects older
adults over the age of 65 years and is, therefore classified as late-onset AD (LOAD). Several risk factors associated with LOAD including the APOE gene have been identified. Moreover, GWAS studies have identified a wide array of genes and polymorphisms that are associated with LOAD risk. Currently, the diagnosis of AD
involves the evaluation of memory and personality changes, cognitive impairment, and medical and family history to rule out other diseases. Laboratory tests to assess the biomarkers in the body fluids as well as MRI, CT, and PET scans to analyse the presence of plaques and NFTs are also included in the diagnosis of AD. It is important to diagnose AD
before the onset of clinical symptoms (ie during the preclinical stage) to delay the progression and for better management of the disease. Research has been conducted to identify biomarkers of AD in the CSF, serum, saliva, and urine during the preclinical stage. Current research has identified several biomarkers and potential biomarkers in the body fluids that enhance diagnostic accuracy. Aside from genetics, other factors
such as diet, physical activity, and lifestyle factors may influence the risk of developing AD. Clinical trials are underway to find potential biomarkers, diagnostic measures, and treatments for AD mainly in the preclinical stage. This review provides an overview of the genes and biomarkers of AD.
Plasma p-tau immunoassays in clinical research for Alzheimer’s disease Teunissen CE, Kolster R, Triana-Baltzer G, Janelidze S, Zeterberg H, Kolb HC. Alzheimers Dement. 2025 Jan; 21 (1): e14397. doi: 10.1002/alz.14397.
The revised biomarker framework for diagnosis and staging of Alzheimer’s disease (AD) relies on amyloid beta (Aβ) and tau pathologies as core markers, and markers for adjacent pathophysiology,
PET scan of normal brain PET scan of Alzheimer’s Disease brain
PET scans showing the differences between a normal older adult’s brain and the brain of an older adult with Alzheimer’s disease.
such as neurodegeneration and inflammation. Many of the core fluid biomarkers are phosphorylated tau (p-tau) fragments, with p-tau217 showing a prominent association with Aβ and tau. While positron emission tomography (PET) imaging is well established, plasma p-tau assays are newer and likely to reduce the use of expensive, and less accessible cerebrospinal fluid (CSF) and PET imaging tests, thereby promoting wider access to AD screening. There is a need for greater understanding of how the various plasma p-tau species reflect different pathological processes of AD and how different immunoassays perform. This review surveys the available immunoassays and highlights their strengths and limitations in different contexts of use. Assays need to be standardised to maximise their impact on AD clinical research, and patient diagnosis and management. Different plasma phosphorylated tau (p-tau) species reflect different pathological processes of Alzheimer’s disease (AD), with p-tau231 showing the greatest association with the earliest increases in brain Aβ accumulation, while p-tau217 shows greater association with both brain Aβ and early tau pathology, and other p-tau and tau fragment species show greater association with later stages of brain tau pathology.
Plasma p-tau217 has proven to
be an excellent biomarker for AD pathology due to its close association with both brain Aβ and tau pathology, as well as its large dynamic range. Many different assays with varying performance exist for the same p-tau species, with mass spectrometry assays
performing uniformly well, and several immunoassays achieving comparable performance. ‘Round robin’ head-to-head studies
have been performed to compare different assays for several key plasma biomarkers, including p-tau181 and p-tau217, but additional head-to-head studies are needed, especially for new analytes and for measuring performance in diverse populations. Plasma immunoassays have the potential to increase accessibility of early diagnostic testing for a broad population, including diverse historically under-represented and under-served populations, due to the potential to be implemented globally, including in primary care setings; however, further research is needed to validate the optimal cut-offs for each assay for real-world clinical usage. Eventually, clinical implementation
of a two-step workflow may allow standalone use of plasma testing in certain contexts, minimising the need for confirmation with costly and less accessible CSF/PET testing.
Diagnostic accuracy of plasma p-tau217/ Aβ42 for Alzheimer’s disease in clinical and community cohorts Wang J, Huang S, Lan G et al.; Translational Biomarker Research of AgIng and Neurodegeneration (TBRAIN). Alzheimers Dement. 2025 Mar; 21 (3): e70038. doi: 10.1002/alz.70038.
This study was undertaken to evaluate the diagnostic performance of a novel plasma phosphorylated tau (p-tau) 217/amyloid beta (Aβ) 42 ratio test for Alzheimer’s disease (AD).
October 2026
WWW.PATHOLOGYINPRACTICE.COM 53
Health and Human Services Department, National Institutes of Health, National Institute on Aging : p.24[1] Public domain Wikimedia Commons
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56
