title: Depression and synaptic zinc regulation in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia.
abstract: OBJECTIVE
  Depression is a common symptom in dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), and Alzheimer disease (AD), yet its molecular basis remains unclear and current antidepressants do not appear to be effective. Cerebral zinc has been implicated in depression and synaptic dysfunction. We investigated the relationship between synaptic zinc regulation (for which zinc transporter 3 [ZnT3] is responsible) and depression in a large clinicopathologic study.
  
  
  METHODS
  We examined brains from people with PDD (N = 29), DLB (N = 27), and AD (N = 15) and comparison subjects without depression or dementia (N = 24). Individuals were categorized according to the presence and severity of depression (on a scale of 0-3) based on standardized assessments during life (principally Neuropsychiatric Inventory). Western blotting was used to determine ZnT3 levels in Brodmann area 9 (BA9), and regression analysis was used to determine the relationship between ZnT3 and depression.
  
  
  RESULTS
  Reductions in ZnT3 in BA9 were significantly associated with elevated depression scores in the study cohort (β = -0.351, df = 93, t = -3.318 p = 0.0004). This association remained when only individuals with DLB, PDD, and no dementia or depression were examined (β = -0.347, df = 78, t = -3.271, p = 0.002) or only individuals with AD and no dementia or depression were examined (β = -0.433, df = 37, t = -2.924, p = 0.006).
  
  
  CONCLUSIONS
  Although decreased zinc levels have been implicated in the genesis of depression in animal models and in major depressive disorder in humans, this study provides the first evidence of a role for zinc in depression in people with dementia and highlights zinc metabolism as a therapeutic target.
authors: King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom.
authors: David R
authors: DR
authors: Whitfield
authors: King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom.
authors: Julie
authors: J
authors: Vallortigara
authors: King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom; Biochemistry Department, College of Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Amani
authors: A
authors: Alghamdi
authors: Department of Neuropathology, Institute of Pathology, University of Debrecen Medical and Health Science Centre, Debrecen, Hungary.
authors: Tibor
authors: T
authors: Hortobágyi
authors: King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom.
authors: Clive
authors: C
authors: Ballard
authors: Newcastle University, Institute for Ageing and Health, Newcastle upon Tyne, United Kingdom.
authors: Alan J
authors: AJ
authors: Thomas
authors: Department of Psychiatry, University of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors: John T
authors: JT
authors: O'Brien
authors: Department of Neurobiology, Ward Sciences and Society, Karolinska Institute, Stockholm, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors: Dag
authors: D
authors: Aarsland
authors: King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom. Electronic address: paul.francis@kcl.ac.uk.
authors: Paul T
authors: PT
authors: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000378:metabolism*; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C102806:SLC30A3 protein, human; D015032:Zinc
keywords: Alzheimer disease; Depression; Lewy body dementia; Parkinson disease dementia; zinc