Prevention of Alzheimer's Disease: A Global Challenge for Next Generation Neuroscientists

Abstract

The incidence of dementia is rapidly increasing in developed countries due to social and demographic changes. This trend is expected to worsen in the coming decades, with the number of cases possibly even tripling in the next 25 years. Therefore Alzheimer's disease (AD) prevention is becoming a global health priority. Our knowledge of the pathophysiological process leading to the development of pathological brain lesions that characterize AD has increased exponentially in recent years. However, the phenotypic expression of AD not only depends on the development of senile plaques and neurofibrillary tangles but other factors also play a role. Thus, over the last few decades, epidemiological studies have revealed several risk factors for developing AD, such as vascular or lifestyle related factors. Having the current knowledge on AD, two different strategies have been developed for the prevention of AD: one is based on primary prevention by acting on modifiable risk factors, the other is a pathophysiology-driven approach aimed to identify individuals in a preclinical stage of the disease and treating them with drugs purporting to act on molecular targets of the amyloid cascade. Several promising trials with these approaches are currently ongoing and results are expected in the next few years. The intrinsic limitations in the design of preventive trials should be overcome through a global effort involving healthy population, healthcare professionals, governments, industry, and scientific institutions. This exertion will be more than compensated if we can make AD a preventable disease.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids

“…Several recent publications suggest health benefits associated with long-term use of antioxidant supplements, including L [ 58, 86, 87 ], and this should be considered (in conjunction with other important lifestyle variables) for healthy aging [ 77, 88, 89 ]. A recent study, for example, suggests a dual strategy for reducing risk for, and progression of, diseases associated with cognitive decline, such as AD; a “primary prevention” approach refers to modification of those risk factors amenable to intervention, in conjunction with screening to identify preclinical disease prior to damage mediated by amyloid plaque deposition [ 90 ]. In a recent letter authored by a panel of experts at the G8 dementia summit [ 91 ], governments of those nations were encouraged to prioritize prevention of dementia as a public health measure.…”

Exogenous phosphatidylglucoside alleviates cognitive impairment by improvement of neuroinflammation, and neurotrophin signaling

“…Dear Editor, Alzheimer's disease (AD) is a commonly progressive disorder of neurodegenerative disease. 1 Until now, no approach to treat the pathological progression of AD has been proven to be effective. 1 Our data favored that the treatment of phosphatidylglucoside (PtdGlc), a novel glucosylated lipid enriched in the brain, protects against Aβ and tau pathology, cognition deficits in APP/PS1 mice, and alleviates neuroinflammation through activation of PPARγ and restoration of the neurotrophin signaling.…”

A Bacterial Component to Alzheimer’s-Type Dementia Seen via a Systems Biology Approach that Links Iron Dysregulation and Inflammagen Shedding to Disease

“…Arguably, the major hurdle in understanding AD is the lack of any integrative and comprehensive knowledge about its etiology and pathogenesis (and there may be many pathways that lead to it), as the onset and risk of AD development is still mostly unexplained (and animal models are of questionable relevance) [ 4 ]. Since our genomes changed but little in the last 50 years, but the incidence of AD increased considerably [ 5 ], this increase can only to a limited extent be explained by genetic factors [ 6, 7 ], notwithstanding the signals detectable in twin and gene association studies [ 8, 9 ]. Although dementia is properly diagnosed via cognitive impairment, and true diagnoses of AD can only be done postmortem, specific lesions that characterize AD include extracellular senile plaques and intracellular neurofibrillary tangles with synaptic and neuronal loss [ 10–13 ].…”