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Alzheimer’s disease is the most common form of dementia. For decades, researchers have sought a treatment to no avail, and our understanding of the condition is now being questioned. This Outlook lays bare the problems, the disagreements and the reasons to be hopeful.
This Nature Outlook is editorially independent. It is produced with third party financial support. About this content.
This Nature Outlook is editorially independent, produced with financial support from a third party.
About
this content.
In this Review, Salter and Stevens discuss the role of microglia in CNS disorders such as autism, neurodegenerative disorders, Alzheimer’s disease, and chronic pain.
Determining how the incidence and prevalence of dementia changes over time requires population-based studies that use consistent methods over time. In this Review, the authors discuss the results of 14 worldwide studies that have attempted this approach. The findings consistently indicate that the incidence and prevalence of dementia, at least in Western countries, is stable or declining.
Therapies for Alzheimer's disease and other neurodegenerative diseases are desperately needed. Yet, a string of disappointments in the neurodegenerative therapy space has meant that several companies over the years have ended their investment in the field. Some companies have diversified their research and development (R&D) models to hedge their bets. Maintaining this diversity to bring down the silos between big pharma and smaller research teams may be necessary to jumpstart and sustain progress in combatting neurodegenerative conditions.
Increasing evidence suggests that Alzheimer disease (AD) is not simply a CNS disorder, but involves interactions between systemic and brain-related factors. Wang and colleagues review the role of amyloid-β (Aβ) in AD, highlighting systemic abnormalities linked to Aβ metabolism and discussing how these abnormalities might influence central pathways of Aβ production and clearance.
There has been a surge in the number of papers discussing the idea that inter-neuronal spread of 'pathogenic' proteins contributes to neurodegenerative disease progression. Walsh and Selkoe provide a critical overview of the evidence for this mechanism, identify gaps in our knowledge and suggest experimental approaches to test the hypothesis.
Amyloid-β (Aβ) and tau come in a variety of forms and assembly states, not all of which are toxic. In this Review, Polanco and colleagues explain the clinical and therapeutic implications of this new understanding while highlighting the physiological and pathogenetic roles of Aβ and tau.
Alzheimer's disease is a progressive, neurodegenerative disorder that affects 10–30% of people >65 years of age. In this Primer, Masters and colleagues describe the pathophysiology of Alzheimer's disease, the advances in diagnostic biomarkers, and the current and future management options.
The hunt for treatments to halt Alzheimer’s disease has been frustrating; it is time to trial preventive drugs, urge Eric McDade and Randall J. Bateman.