Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Abstract

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease (AD) and associated socioeconomic burdens. Abnormal metabolism of amyloid-β (Aβ) has been proposed as a significant pathomechanism in AD, supported by results of recent clinical trials using anti-Aβ antibodies. Nonetheless, the cognitive benefits of the current treatments are limited. The etiology of AD is multifactorial, encompassing Aβ and tau accumulation, neuroinflammation, demyelination, vascular dysfunction, and comorbidities, which collectively lead to widespread neurodegeneration in the brain and cognitive impairment. Hence, solely removing Aβ from the brain may be insufficient to combat neurodegeneration and preserve cognition. To attain effective treatment for AD, it is necessary to (1) conduct extensive research on various mechanisms that cause neurodegeneration, including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level; (2) identify neuroprotective intervention targets against different neurodegeneration mechanisms; and (3) discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients. The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated, multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD. The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD, with the goal of halting or even reversing cognitive decline.

Keywords: Alzheimer's disease; early intervention; neural regeneration; neuroprotection; systematic perspective.

Figure 1

Neuroprotective interventions for AD. Main neuroprotective intervention targets for AD, including NTFs, antineuroinflammation, astrocytic protection, remyelination, stem‐cell therapy and in vivo neural regeneration, glucose metabolism regulation, vascular system protection, lymphatic protection, prion‐like proteinopathy regulation, peripheral neurotoxic substances clearance, systemic NTFs, and physical exercise, as well as food and nutrition. Investigations into advanced neuroimaging techniques for earlier and more precise characterization of molecular events at scales ranging from cellular to full system level are equally important as it is necessary for the evaluation of the beneficial effects of different neuroprotective intervention approaches. AD, Alzheimer's disease; CNTF, ciliary neurotrophic factor; DHA, docosahexaenoic acid; GDF11, growth differentiation factor 11; GDNF, glial cell‐derived neurotrophic factor; IFN‐γ, interferon‐γ; NTFs, neurotrophic factors; ROS, reactive oxygen species; TNF‐α, tumor necrosis factor‐α.