Progress on early diagnosing Alzheimer’s disease

doi:10.1007/s11684-023-1047-1

Front. Med.

2024, Vol. 18

Issue (3) : 446-464 https://doi.org/10.1007/s11684-023-1047-1

Progress on early diagnosing Alzheimer’s disease

Yixin Chen¹, Murad Al-Nusaif¹, Song Li¹, Xiang Tan¹, Huijia Yang¹, Huaibin Cai², Weidong Le^1,³(

)

¹. Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
². Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
³. Institute of Neurology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions. The disease follows a continuum, starting with preclinical stages, progressing to mild cognitive and behavioral impairment, ultimately leading to dementia. Early detection of AD is crucial for better diagnosis and more effective treatment. However, the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive, and mostly are still not able to detect early disease state. Consequently, there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD. Various non-cognitive manifestations, including behavioral abnormalities, sleep disturbances, sensory dysfunctions, and physical changes, have been observed in the preclinical AD stage before occurrence of notable cognitive decline. Recent research advances have identified several biofluid biomarkers as early indicators of AD. This review focuses on these non-cognitive changes and newly discovered biomarkers in AD, specifically addressing the preclinical stages of the disease. Furthermore, it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

Keywords Alzheimer’s disease early diagnosis non-cognitive symptoms biomarkers

Corresponding Author(s): Weidong Le

Just Accepted Date: 18 March 2024 Online First Date: 20 May 2024 Issue Date: 17 June 2024

Cite this article:

Yixin Chen,Murad Al-Nusaif,Song Li, et al. Progress on early diagnosing Alzheimer’s disease[J]. Front. Med., 2024, 18(3): 446-464.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-023-1047-1
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I3/446

Fig.1 Non-cognitive manifestation and clinical biomarkers in the preclinical stage of AD are addressed in this review. ↑, increase. ↓, decrease. *The symptom is solely based on animal studies, lacking clinical evidence. Abbreviations: BPSD, behavioral and psychological symptoms of dementia; CRD, circadian rhythm disruptions; NREM, non-rapid eye movement; EEG, electroencephalogram; ERG, electroretinography; Aβ, amyloid-beta; PET, positron emission tomography; T-tau, total-tau protein; P-tau, phosphorylated-tau protein; NfL, neurofilament light chain; GFAP, glial fibrillary acidic protein; HSV, herpes simplex virus; P. gingivalis, Porphyromonas gingivalis;AD, Alzheimer’s disease. (The graphic was created with BioRender.com.)

Fig.2 Clinical tactic for early diagnosis, prevention, and treatment in the preclinical stage of AD. (A) Main pathological changes in preclinical AD. (B) Non-cognitive manifestations in the preclinical stage of AD. (C) Main biomarkers in preclinical AD. Abbreviations: AD, Alzheimer’s disease; BPSD, behavioral and psychological symptoms of dementia; Aβ, amyloid-beta; T-tau, total-tau protein; P-tau, phosphorylated-tau protein; miRNA, microRNA. (The graphic was created with BioRender.com.)

Fig.3 Historical review of AD diagnosis. Abbreviations: NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association; AD, Alzheimer’s disease; PET, positron emission tomography; CSF, cerebrospinal fluid; IWG, International Working Group; NIA-AA, National Institute on Aging and the Alzheimer’s Association; A, amyloid; T, pathologic tau; N, neurodegeneration; Aβ, amyloid-beta; GFAP, glial fibrillary acidic protein; NfL, neurofilament light chain. (The graphic was created with BioRender.com.)

Tab.1 Novel imaging techniques for early diagnosis of AD

Tab.2 Longitudinal study data of non-cognitive symptoms

Tab.3 Longitudinal study data of biomarkers

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