Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

被引:1892
作者
Long, Justin M. [1 ]
Holtzman, David M. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Neurol,Hope Ctr Neurol Disorders, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
关键词
AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; SIMPLEX-VIRUS TYPE-1; A-BETA CLEARANCE; RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; PAIRED HELICAL FILAMENTS; ANTI-TAU ANTIBODY; SLOW-WAVE SLEEP;
D O I
10.1016/j.cell.2019.09.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular beta-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphosphylated tau as neurofibrillary tangles remaim. the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease-modifying treatment currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here, we review recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies.
引用
收藏
页码:312 / 339
页数:28
相关论文
共 320 条
  • [1] Microbiome-microglia connections via the gut-brain axis
    Abdel-Haq, Reem
    Schlachetzki, Johannes C. M.
    Glass, Christopher K.
    Mazmanian, Sarkis K.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2019, 216 (01) : 41 - 59
  • [2] Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial
    不详
    [J]. LANCET NEUROLOGY, 2008, 7 (01) : 41 - 49
  • [3] A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity
    Ahmed, Zeshan
    Cooper, Jane
    Murray, Tracey K.
    Garn, Katya
    McNaughton, Emily
    Clarke, Hannah
    Parhizkar, Samira
    Ward, Mark A.
    Cavallini, Annalisa
    Jackson, Samuel
    Bose, Suchira
    Clavaguera, Florence
    Tolnay, Markus
    Lavenir, Isabelle
    Goedert, Michel
    Hutton, Michael L.
    O'Neill, Michael J.
    [J]. ACTA NEUROPATHOLOGICA, 2014, 127 (05) : 667 - 683
  • [4] Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression - A randomized controlled trial
    Aisen, PS
    Schafer, KA
    Grundman, M
    Pfeiffer, E
    Sano, M
    Davis, KL
    Farlow, MR
    Jin, S
    Thomas, RG
    Thal, LJ
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (21): : 2819 - 2826
  • [5] A randomized controlled trial of prednisone in Alzheimer's disease
    Aisen, PS
    Davis, KL
    Berg, JD
    Schafer, K
    Campbell, K
    Thomas, RG
    Weiner, MF
    Farlow, MR
    Sano, M
    Grundman, M
    Thal, LJ
    [J]. NEUROLOGY, 2000, 54 (03) : 588 - 593
  • [6] Regional brain hypometabolism is unrelated to regional amyloid plaque burden
    Altmann, Andre
    Ng, Bernard
    Landau, Susan M.
    Jagust, William J.
    Greicius, Michael D.
    [J]. BRAIN, 2015, 138 : 3734 - 3746
  • [7] 2018 Alzheimer's disease facts and figures
    不详
    [J]. ALZHEIMERS & DEMENTIA, 2018, 14 (03) : 367 - 425
  • [8] [Anonymous], CELL
  • [9] Depletion of microglia and inhibition of exosome synthesis halt tau propagation
    Asai, Hirohide
    Ikezu, Seiko
    Tsunoda, Satoshi
    Medalla, Maria
    Luebke, Jennifer
    Haydar, Tank
    Wolozin, Benjamin
    Butovsky, Oleg
    Kuegler, Sebastian
    Ikezu, Tsuneya
    [J]. NATURE NEUROSCIENCE, 2015, 18 (11) : 1584 - 1593
  • [10] Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease
    Aschenbrenner, Andrew J.
    Gordon, Brian A.
    Benzinger, Tammie L. S.
    Morris, John C.
    Hassenstab, Jason J.
    [J]. NEUROLOGY, 2018, 91 (09) : E859 - E866