Depression and Alzheimer's disease: Neurobiological links and common pharmacological targets

Filippo Caraci, Agata Copani, Ferdinando Nicoletti, Filippo Drago

Research output: Contribution to journalArticle

Abstract

Depression is one of the most prevalent and life-threatening forms of mental illnesses, whereas Alzheimer's disease is a neurodegenerative disorder that affects more than 37 million people worldwide. Recent evidence suggests a strong relationship between depression and Alzheimer's disease. A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer's disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer's disease brain, are more pronounced in the brains of Alzheimer's disease patients with comorbid depression as compared with Alzheimer's disease patients without depression. On the other hand, neurodegenerative phenomena have been observed in different brain regions of patients with a history of depression. Recent evidence suggests that molecular mechanisms and cascades that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis, are also involved in the pathogenesis of Alzheimer's disease. In particular, a specific impairment in the signaling of some neurotrophins such as transforming-growth-factor β1 (TGF-β1) and brain-derived neurotrophic factor (BDNF) has been observed both in depression and Alzheimer's disease. In the present review we will examine the evidence on the common molecular pathways between depression and Alzheimer's disease and we will discuss these pathways as new pharmacological targets for the treatment of both major depression and Alzheimer's disease.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalEuropean Journal of Pharmacology
Volume626
Issue number1
DOIs
Publication statusPublished - Jan 10 2010

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Brain-derived neurotrophic factor
  • Chronic inflammation
  • Major depression
  • Neuroprotection
  • Transforming-growth-factor-β1

ASJC Scopus subject areas

  • Pharmacology

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