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Alzheimers Dement (N Y). 2016 Sep 20;3(1):83-91. doi: 10.1016/j.trci.2016.09.002. eCollection 2017 Jan.

Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development.

Author information

1
Memory & Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
2
Division of Medical & Scientific Relations, Alzheimer's Association, Chicago IL, USA.
3
Merck, Kenilworth, NJ, USA.
4
Piramal Pharma, Inc., Boston, MA, USA.
5
Bracket Global, Wayne, PA, USA.
6
Quintiles (formerly), Rockville, MD, USA.
7
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA.
8
MedAvante, Hamilton, NJ, USA.
9
Department of Neurology, Loyola University Medical Center, Maywood, IL, USA.
10
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
11
European Medicines Agency (EMA), London, UK.
12
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
13
Department of Neurology, Skåne University Hospital, Lund, Sweden.
14
Independent Science Writer, Elverson, PA, USA.
15
Eli Lilly & Co., Indianapolis, IN, USA.

Abstract

Dementia is often characterized as being caused by one of several major diseases, such as Alzheimer's disease (AD), cerebrovascular disease, Lewy body disease, or a frontotemporal degeneration. Failure to acknowledge that more than one entity may be present precludes attempts to understand interactive relationships. The clinicopathological studies of dementia demonstrate that multiple pathologic processes often coexist. How overlapping pathologic findings affect the diagnosis and treatment of clinical AD and other dementia phenotypes was the topic taken up by the Alzheimer's Association's Research Roundtable in October 2014. This review will cover the neuropathologic basis of dementia, provide clinical perspectives on multiple pathologies, and discuss therapeutics and biomarkers targeting overlapping pathologies and how these issues impact clinical trials.High prevalence of multiple pathologic findings among individuals with clinical diagnosis of AD suggests that new treatment strategies may be needed to effectively treat AD and other dementing illnesses.

KEYWORDS:

Alzheimer's disease (AD); Cerebrovascular disease; Frontotemporal degeneration; Lewy body disease; TDP-43; Tau; α-Synuclein; β-amyloid

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