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Definition and Pathological Features

Alzheimer’s disease (AD), the most common cognitive disorder, is marked by cognitive decline, neuropsychiatric symptoms, and a progressive loss of social and daily functioning. Its key pathological features are amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. Aβ deposition can begin up to 30 years before clinical symptoms, starting in the neocortex and spreading to other brain regions. Tau phosphorylation follows a Braak staging pattern, leading to hypometabolism, hippocampal atrophy, and cortical thinning. As of 2024, AD is redefined as a biological brain aging process identifiable by biomarkers, even without clinical symptoms.

Epidemiology

In China, a 2020 survey estimated 38.77 million individuals aged 60 and above have Mild Cognitive Impairment (MCI), and 15.07 million have dementia, with about 9.83 million being AD patients. The prevalence of MCI in those aged 55 and above is 12.2%, with amnestic MCI (aMCI) at 10.9%. MCI is more prevalent in women, rural residents, individuals living alone, and those with lower education.

Genetics 

AD can be sporadic or familial. Familial AD, linked to mutations in PSEN1, PSEN2, or APP genes, is rare and usually early-onset (40–60 years). Less than 5% of AD cases are early-onset or familial, while most are late-onset and sporadic. Individuals with Down syndrome are at higher risk of AD due to APP gene triplication.

Diagnostic Framework and Biomarkers

In 2024, the NIA and AA updated the diagnostic framework, emphasizing biomarkers. Core biomarkers include Aβ PET imaging, CSF Aβ42/40 ratio, and plasma p-tau217 levels. Plasma-based assays are becoming key clinical tools. AD is categorized into seven stages, from Stage 0 to Stage 6, providing a treatment roadmap.

Treatment Approaches

- Early Stage (MCI): Anti-Aβ disease-modifying therapies (DMTs).  

- Mild AD Dementia: Medications like donepezil and galantamine.  

- Moderate to Severe AD: Combined pharmacological treatment and enhanced caregiving.

Research and Treatment Advances*

AD research is moving toward precision medicine. Advances in blood-based biomarker detection, such as immunoprecipitation–mass spectrometry (IP-MS), enable earlier screening. Novel therapies targeting tau pathology and gene therapies are emerging. Preventive treatment is gaining attention for asymptomatic individuals with pathogenic mutations. Multi-omics data integration and AI technologies hold promise for ultra-early diagnosis and precise intervention, improving patient outcomes.

References

[1] Chinese Consensus on the Diagnosis and Treatment of Alzheimer's Disease–Related Mild Cognitive Impairment (2024).  

[2] Clifford Jack R Jr, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. *Alzheimers Dement*. 2024.8(1).  

[3] Blood biomarkers for Alzheimer’s disease in clinical practice and trials.  

[4] Blood-based biomarkers for Alzheimer’s disease.

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