Affiliations: [a] Department of Neurology, Center for Cognitive Neurology, NYU School of Medicine, New York, NY, USA
| [b] Departments of Neurology, Pathology and Psychiatry, Center for Cognitive Neurology, NYU School of Medicine, New York, NY, USA
Correspondence:
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Correspondence to: Thomas Wisniewski, Departments of Neurology, Pathology and Psychiatry, Center for Cognitive Neurology, YU School of Medicine, Alexandria ERSP, Rm 802, 450 East 29th Street, New York, NY, 10016 USA. E-mail: Thomas.wisniewski@nyumc.org.
Abstract: There is growing genetic and proteomic data highlighting the complexity of Alzheimer’s disease (AD) pathogenesis. Greater use of unbiased “omics” approaches is being increasingly recognized as essential for the future development of effective AD research, that need to better reflect the multiple distinct pathway abnormalities that can drive AD pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. We highlight our recent efforts to increase use of human tissue to gain a better understanding of the AD pathogenesis subtype variety and to develop several distinct therapeutic approaches tailored to address this diversity. These therapeutic approaches include the blocking of the Aβ/apoE interaction, stimulation of innate immunity, and the simultaneous blocking of Aβ/tau oligomer toxicity. We believe that future successful therapeutic approaches will need to be combined to better reflect the complexity of the abnormal pathways triggered in AD pathogenesis.
