Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and accounts for most cases of dementia. The prevalence of AD has increased in the current rapidly aging society and contributes to a heavy burden on families and society. Despite the profound impact of AD, current treatments are unable to achieve satisfactory therapeutic effects or stop the progression of the disease. Finding novel treatments for AD has become urgent. In this paper, we reviewed novel therapeutic approaches in five categories: anti-amyloid therapy, anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, and brain stimulation. The trend of therapeutic development is shifting from a single pathological target to a more complex mechanism, such as the neuroinflammatory and neurodegenerative processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), also have the potential for clinical application. In the future, it is possible for physicians to choose appropriate interventions individually on the basis of precision medicine.
Highlights
Published: 30 July 2021Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia in the elderly [1]
Glial activation is associated with the signaling pathways of apolipoprotein E (ApoE), triggering the receptor expressed on myeloid cells 2 (TREM2), Toll-like receptor (TLR), and colonystimulating factor-1 receptor (CSF1R) (Figure 1, panel A) [199]
The results showed that repetitive transcranial magnetic stimulation (rTMS) had advantages in the treatment of mild AD, with better performance in memory and language in the treated group than the sham group
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia in the elderly [1]. Around 50 million people have dementia, and 50–70% of cases are attributed to AD [2,3] Both the prevalence and incidence of AD increase with age. The population aged 65 years or older is expected to increase from 9.3% in 2020 to around 16.0% in 2050 [4]. Patients with AD develop behavioral and psychological symptoms of dementia (BPSD), including delusions, misperceptions, mood disorders, and behavioral disturbances [9]. The heavy care burden of AD leads to physical, psychological, and financial impacts on both families and society. AChEIs only show modest efficacy on cognitive deficits and non-significant efficacy on functional capacity in mild to moderate AD [13]. This article aims to review novel therapeutic approaches to AD, including pharmacological interventions (Table 1) and non-pharmacological interventions (Table 2)
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