However, the complexities of NE signaling and multiplicity of effects of adrenergic receptor subtypes, together with the limitations of animal studies, underscore the importance of translating these studies to humans. The availability of clinically approved drugs that enhance kinase inhibitor Ruxolitinib central nor adrenergic function provides a timely opportunity to repurpose their use to determine their potential as a novel disease-modifying therapeutic strategy. Abbreviations A??: amyloid-beta; AD: Alzheimer’s disease; APP: amyloid precursor protein; DBH: dopamine ??-hydroxylase; DBH-/-: dopamine ??-hydroxylase knockout; dsp-4: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; IL: interleukin; LC: locus coeruleus; L-DOPS: L-threo-3:4-dihydroxyphenylserine; LTP: long-term potentiation; MCI: mild cognitive impairment; NE: norepinephrine; NET: norepinephrine transporter; NET KO: norepinephrine transporter knockout; NET WT: norepinephrine transporter wildtype; NF: nuclear factor; PS1: presenilin-1; SNP: single nucleotide polymorphism; TNF: tumor necrosis factor.

Competing interests TC, BK, MPK, TH, MTH, DW and AIL declare that they have no competing interests. WTH received one compensated meal from Eli Lilly as part of the Alzheimer’s Association International Conference (under $100). WTH has patents pending Anacetrapib on cerebrospinal fluid biomarkers for frontotemporal lobar degeneration and plasma biomarkers for AD. Some markers in these panels overlap with cerebrospinal fluid biomarkers to be measured in the atomoxetine trial. Authors’ contributions All authors contributed to the writing and editing of the manuscript.

MTH and MPK selleckbio generated the data presented in Figure ?Figure11. Acknowledgements TC is supported by the Alzheimer’s Disease Research Center (ADRC; 5P50 “type”:”entrez-nucleotide”,”attrs”:”text”:”AG025688″,”term_id”:”6624379″,”term_text”:”AG025688″AG025688, PI AIL). The ADRC supported writing of the manuscript. DW received funding from the Alzheimer’s Drud Discovery Foundation and the ADRC for design, collection, analysis and interpretation of data. The ADRC supported writing of the manuscript. AIL has funding from the Alzheimer’s Drug Discovery Foundation and philanthropic funds for the phase II clinical trial with atomoxetine. Funding from the Alzheimer’s Drug Discovery Foundation, the ADRC and philanthropy supported the writing of the manuscript.
Alzheimer’s disease (AD), the most common cause of dementia among older people, is characterized by behavioral disorders and a progressive decline in memory function. Senile plaques, neurofibrillary tangles, and cholinergic dysfunction are major hallmarks of the disease.