LITERATURE UPDATE


Alzheimer’s disease: a selection of recent research into biomarkers and genetic factors


Alzheimer’s disease is the most common cause of dementia, presenting as a gradual decline in memory, thinking, behaviour and social skills. New tests might be able to diagnose the disease when symptoms are very mild, so that the latest therapeutic advances in the field can be applied. Here, Pathology in Practice Science Editor Brian Nation compiles a small selection of current research interest.


Alzheimer’s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs Monteiro AR, Barbosa DJ, Remião F, Silva R. Biochem Pharmacol. 2023 May; 211: 115522. doi: 10.1016/j. bcp.2023.115522.


Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions of people worldwide, with both prevalence and incidence increasing with age. It is characterised by cognitive decline associated, specifically, with degeneration of cholinergic neurons. The problem of this disease is even


more fundamental as the available therapies remain fairly limited and mainly focused on symptom relief. Although the


aetiology of the disease remains elusive, two main pathological hallmarks are described: i) presence of neurofibrillary tangles formed by unfolded protein aggregates (hyperphosphorylated Tau protein) and ii) presence of extracellular aggregates of amyloid-beta peptide. Given the complexity surrounding the pathogenesis of the disease, several potential targets have been highlighted and interrelated upon its progression, such as oxidative stress and the accumulation of metal ions. Thus, advances have been made on the development of innovative multitarget therapeutic compounds to delay the disease progression and restore cell function. This review focuses on the ongoing


research on new insights and emerging disease-modifying drugs for AD treatment. Furthermore, classical and


novel potential biomarkers for early diagnosis of the disease, and their role in assisting the improvement of targeted therapies are also be approached.


Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer’s disease Stevenson-Hoare J, Heslegrave A, Leonenko G et al. Brain. 2023 Feb 13; 146 (2): 690–9. doi: 10.1093/brain/awac128.


Plasma biomarkers for Alzheimer’s disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer’s disease with biomarkers rather than clinical assessment, the authors assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer’s disease instead of the risk of dementia.


In a cohort of Alzheimer’s disease


Alzheimer’s disease: histopathology showing an amyloid plaque in the brain (haematoxylin and eosin [H&E] staining).


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cases (n = 1439, mean age 68 years [standard deviation = 8.2]) and screened controls (n = 508, mean age 82 years [standard deviation = 6.8]), the authors measured plasma concentrations of the 40 and 42 amino acid-long amyloid-β (Aβ) fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) using state-of-the-art single molecule array (Simoa) technology. They tested the relationships between the biomarkers and Alzheimer’s disease genetic risk, age at onset, and disease duration. They also conducted a genome-wide association


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Mikael Häggström CC0 Wikimedia Commons


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