Precision medicine and drug development in Alzheimer's disease: the importance of sexual dimorphism and patient stratification

Article ID	Journal	Published Year	Pages	File Type
10212275	Frontiers in Neuroendocrinology	2018	64 Pages	PDF

Abstract

We hypothesize that sex and gender differences, extending from genetic to psychosocial domains, are highly relevant for the understanding of AD pathophysiology, and for the conceptualization of basic/translational research and for clinical therapy trial design.

Keywords

NSAIDS DHT PCC NSE IDM CDC EMA COX-2 iNOS CRF IOM APP IL-1β DTI NGF MMSE NMDA N-methyl-d-aspartate Aβ1-42 MnSOD NAcc AChEIs OVX NIH trkA CMRGlc RCTs GPR30 GPER GRC KEEPS mCsA 18F-FDG-PET Amyloid PET imaging tropomyosin receptor kinase A t-tau Nuclear estrogen receptors FDA WHIMS BDNF Mitochondrial DNA Neuron-specific enolase G protein-coupled estrogen receptor MAPK mERs NFκB PPARs ROS Clinical trials Randomized controlled trials Apoe apolipoprotein E European Medicines agency Women’s Health Initiative Alzheimer’s Disease Neuroimaging Initiative mild cognitive impairment Subjective cognitive impairment MRI Ovariectomy U.S. Centers for Disease Control and Prevention Interleukin-1-beta Alzheimer’s disease Neurodegenerative disease diffusion tensor imaging Magnetic resonance imaging Total tau long-term potentiation LTP tumor necrosis factor-alpha Positron emission tomography Gender Sex Non-steroidal anti-inflammatory drugs estrogen replacement therapy Dihydrotestosterone Sexual dimorphism mtDNA Systems biology Food and Drug Administration manganese-dependent superoxide dismutase Cyclooxygenase-2 PMI corticotropin-releasing factor sci nerve growth factor Brain-derived neurotrophic factor TNF-α nuclear factor kappa-light-chain-enhancer of activated B cells posterior cingulate cortex Cerebrospinal fluid CSF Genome-wide association studies GWAS Mini-Mental State Examination acetylcholinesterase inhibitors National Institute of Health Institute of Medicine Knock-in mice Cerebral metabolic rate of glucose Biomarkers nitric oxide synthase ERT nucleus basalis MCI Homeostasis whi PET amyloid precursor protein mitogen-activated protein kinase Precision medicine Single nucleotide polymorphism ChAT SNP ADNI choline acetyltransferase Reactive oxygen species Peroxisome proliferator-activated receptors membrane estrogen receptors G protein-coupled receptor 30