Alzheimer’s disease: a scoping review of biomarker research and development for effective disease diagnosis

ABSTRACT

Introduction

Alzheimer’s disease (AD) is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population. Characterized by extracellular accumulation of amyloid-beta (Aβ), intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition. Amyloid/tau/neurodegeneration (ATN) classification is utilized for research purposes and involves amyloid, tau, and neuronal injury staging through MRI, PET scanning, and CSF protein concentration estimations. CSF sampling is invasive, and MRI and PET scanning requires sophisticated radiological facilities which limit its widespread diagnostic use. ATN classification lacks effectiveness in preclinical AD.

Areas Covered

This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments.

Expert Opinion

It is an accepted observation that AD-related pathological changes occur over a long period of time before the first symptoms are observed providing ample opportunity for detection of biological alterations in various biological samples that can aid in early diagnosis and modify treatment outcomes.

KEYWORDS:

• Alzheimer’s disease
• biomarkers
• β-amyloid
• tau
• neuronal injury
• miRNA
• proteomics
• metabolomics
• artificial intelligence (AI)
• machine learning (ML)

Article highlights

• Alzheimer’s disease is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population, characterized by extracellular accumulation of amyloid-beta (Aβ), and intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition.

• Biomarkers are reckonable characteristics that are robust, simple, accurate, and inexpensive with sensitivity and specificity greater than 80%.

• Ideal biological samples utilized should be blood and urine due to ease of collection, resampling, and processing.

• ATN research classification is utilized in AD that categorizes the pathological hallmarks of Alzheimer’s disease into ATN where A stands for Amyloid deposits, T stands for Neurofibrillary tangles and N stands for neurologic injury and neurodegeneration. The grading involves the presence or absence of the pathologic hallmark, examined through MRI, PET, and CSF peptide concentration evaluation. It does not consider any signs of clinical manifestation. ATN classification lacks effectiveness in preclinical AD.

• To aid research and development in the Alzheimer’s disease domain, a new arsenal of biomarkers from different biological samples like blood, urine, tears, and saliva that are easily collected, processed, and allow repeated sampling is required for efficient Alzheimer’s disease screening, diagnosis, prognosis, and monitoring of AD treatments.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.