Clinical Research on Alzheimer's Disease: Progress and Perspectives

Abstract

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.

Keywords: 5-HT6 receptor antagonist; Alzheimer’s disease; Amyloid-beta; BACE1 inhibitor; Biomarker; Immunotherapy; Positron emission tomographic imaging; Primary prevention; Tau.

Fig. 1

High performance of different plasma biomarkers. A ROC analyses of different biomarkers to predict the states of Aβ+/Aβ− for the discovery and validation data sets. Unadjusted analyses of the National Center for Geriatrics and Gerontology from the Japanese (NCGG) PIB-PET discovery data (left), the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) PIB-PET data (middle), and AIBL overall (right) validation data. B Comparisons of the performances of the above biomarkers corresponding to the ROC curves. Statistically significant differences between two AUCs are indicated by asterisks. *^,†,‡P < 0.05; **^{,††,‡‡}P < 0.01; ***^{,†††,‡‡‡}P < 0.001. (Figures adapted from Nakamura et al. [15] with permission)

Fig. 2

Annualized incidence rates showing the instantaneous hazard as a function of polygenic hazard score percentile and age. PHS, polygenic hazard score. (Image adapted from Desikan et al. [24] with permission)

Fig. 3

Life-course model of contributions of modifiable risk factors to dementia. Percentages are presented as potentially modifiable or non-modifiable risk factors. (Image adapted from Livingston et al. [2] with permission)