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Nature Neuroscience presents a collection of Reviews on recent advances in neurodegenerative disease, highlighting shared mechanisms across diseases and the gaps in our knowledge that still need to be addressed.
Neurodegenerative diseases cause progressive loss of brain functions associated with aging. Here we review intricate genotype–phenotype relationships, shared pathogenic mechanisms, and emerging therapeutic opportunities and challenges.
Older people often have more than one form of neuropathology. The authors describe how insights from the genomic architecture of syndromically defined neurodegenerative diseases can be integrated to inform person-specific trajectories of brain aging.
Adequate blood supply and vascular integrity are key to normal brain functioning. Cerebral blood flow and blood–brain barrier disruption contribute to Alzheimer’s disease and other neurodegenerative disorders as reviewed in humans and animal models.
A newly recognized process in neurodegenerative disease is accumulation of misfolded protein aggregates that self-replicate to spread damage between cells and tissues. This process has implications in designing strategies for treatment and diagnosis.
Many neurodegenerative diseases involve the seeded propagation and spread of abnormally shaped proteins within the nervous system. The resulting disease reflects the interaction between the misfolded proteins and the host milieu.
Neurodegenerative diseases impact specific cell populations within the brain. However, not all cells within the population are impacted, a phenomenon called selective cellular vulnerability. The molecular basis of this vulnerability is discussed.
Microglia are the sentinels, housekeepers, and defenders of the brain. In this review we consider the immune checkpoints that control microglial functions and discuss how their imbalance and subsequent neuroinflammation leads to neurodegeneration.
The authors review the current state of rodent models for AD, PD, FTD, and ALS. Limitations and utility of current models, issues regarding translatability, and future directions for developing animal models of these human disorders are discussed.
