Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

Authors:
Dr. Atoossa Fahimi, MD, PsyM
Dr. Atoossa Fahimi, MD, PsyM
Stanford University School of Medicine
Postdoc Fellow/ Research Associate
Psychiatry-Neuroscience
Palo Alto, CA | United States
Dr.  Cristy Phillips, PT, MSPT, SCCD, EdD
Dr. Cristy Phillips, PT, MSPT, SCCD, EdD
Arkansas State University
Assistant Professor
Rehabilitation
Jonesboro , AR | United States
Prof Ahmad Salehi, M.D., Ph.D.
Prof Ahmad Salehi, M.D., Ph.D.
Stanford University School of Medicine
Professor
Palo Alto, CA | United States

Curr Alzheimer Res 2016 ;13(1):68-83

Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, VA Palo Alto Health Care System, 3801 Miranda Ave, 151Y, Palo Alto, CA 94304, USA.

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

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Source
http://dx.doi.org/10.2174/1567205012666150921095924DOI Listing
September 2016
9 Reads
10 Citations
3.890 Impact Factor

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