Focus |

Focus on neurodegenerative diseases

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.

Editorial

Reviews

  • Nature Neuroscience | Review Article

    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.

    • Li Gan
    • , Mark R. Cookson
    • , Leonard Petrucelli
    •  &  Albert R. La Spada
  • Nature Neuroscience | Review Article

    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.

    • Philip L. De Jager
    • , Hyun-Sik Yang
    •  &  David A Bennett
  • Nature Neuroscience | Review Article

    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.

    • Melanie D. Sweeney
    • , Kassandra Kisler
    • , Axel Montagne
    • , Arthur W. Toga
    •  &  Berislav V. Zlokovic
  • Nature Neuroscience | Review Article

    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.

    • Hongjun Fu
    • , John Hardy
    •  &  Karen E. Duff

From the archive

  • Nature Neuroscience | Article

    The authors constructed and validated a molecular network of the aging human cortex from RNA sequencing data from 478 individuals and identified genes that affect cognitive decline or neuropathology in Alzheimer’s disease.

    • Sara Mostafavi
    • , Chris Gaiteri
    • , Sarah E. Sullivan
    • , Charles C. White
    • , Shinya Tasaki
    • , Jishu Xu
    • , Mariko Taga
    • , Hans-Ulrich Klein
    • , Ellis Patrick
    • , Vitalina Komashko
    • , Cristin McCabe
    • , Robert Smith
    • , Elizabeth M. Bradshaw
    • , David E. Root
    • , Aviv Regev
    • , Lei Yu
    • , Lori B. Chibnik
    • , Julie A. Schneider
    • , Tracy L. Young-Pearse
    • , David A. Bennett
    •  &  Philip L. De Jager
  • Nature Neuroscience | Article

    TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD, leading to aberrant Mapt splicing and a paucity of parvalbumin interneurons. Phenotypic heterogeneity is exploited to yield modifiers of disease.

    • Matthew A. White
    • , Eosu Kim
    • , Amanda Duffy
    • , Robert Adalbert
    • , Benjamin U. Phillips
    • , Owen M. Peters
    • , Jodie Stephenson
    • , Sujeong Yang
    • , Francesca Massenzio
    • , Ziqiang Lin
    • , Simon Andrews
    • , Anne Segonds-Pichon
    • , Jake Metterville
    • , Lisa M. Saksida
    • , Richard Mead
    • , Richard R Ribchester
    • , Youssef Barhomi
    • , Thomas Serre
    • , Michael P. Coleman
    • , Justin R. Fallon
    • , Timothy J. Bussey
    • , Robert H. Brown Jr
    •  &  Jemeen Sreedharan
  • Nature Neuroscience | Article | open

    By comparing the genome-wide profile of H4K16ac in AD with younger and elder controls, the authors propose a mechanism for how age is a risk factor for AD: a histone modification, whose accumulation is associated with aging, is dysregulated in AD.

    • Raffaella Nativio
    • , Greg Donahue
    • , Amit Berson
    • , Yemin Lan
    • , Alexandre Amlie-Wolf
    • , Ferit Tuzer
    • , Jon B. Toledo
    • , Sager J. Gosai
    • , Brian D. Gregory
    • , Claudio Torres
    • , John Q. Trojanowski
    • , Li-San Wang
    • , F. Brad Johnson
    • , Nancy M. Bonini
    •  &  Shelley L. Berger
  • Nature Neuroscience | Article

    Using an inducible mouse model of sporadic ALS, Spiller et al. show that spinal microgliosis is not a major feature of TDP-43-triggered disease. Instead, microglia mediate TDP-43 clearance and motor recovery, suggesting a neuroprotective role in ALS.

    • Krista J. Spiller
    • , Clark R. Restrepo
    • , Tahiyana Khan
    • , Myrna A. Dominique
    • , Terry C. Fang
    • , Rebecca G. Canter
    • , Christopher J. Roberts
    • , Kelly R. Miller
    • , Richard M. Ransohoff
    • , John Q. Trojanowski
    •  &  Virginia M.-Y. Lee