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Alzheimer Disease: Mechanistic Understanding Predicts Novel Therapies

2004; American College of Physicians; Volume: 140; Issue: 8 Linguagem: Inglês

10.7326/0003-4819-140-8-200404200-00047

1539-3704

Dennis J. Selkoe,

Cholinesterase and Neurodegenerative Diseases

Reviews20 April 2004Alzheimer Disease: Mechanistic Understanding Predicts Novel TherapiesDennis J. Selkoe, MDDennis J. Selkoe, MDFrom Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-8-200404200-00047 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAlzheimer disease usually begins with gradual failure of recent memory with preserved alertness and motor function.The syndrome of minimal cognitive impairment (mild cognitive impairment)—a subtle decrease in short-term declarative memory with otherwise normal cognition—is often a harbinger of Alzheimer disease.Alzheimer disease progresses slowly to involve many cognitive spheres and shortens life expectancy, with most patients ultimately dying of secondary respiratory complications (for example, aspiration and pneumonia).Treatment with acetylcholinesterase inhibitors can temporarily alleviate some symptoms but does not modify disease progression.A noncompetitive N-methyl-d-aspartate–receptor antagonist (memantine) has recently been approved as a noncholinergic symptomatic treatment.Epidemiologic data suggest that long-term use of ...References1. 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[PMID: 11430801] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.For definition of terms used, see Glossary.Acknowledgments: The author thanks his colleagues and collaborators for many helpful discussions.Grant Support: By the National Institutes of Health, Alzheimer's Association, and the Foundation for Neurologic Diseases. Dr. Selkoe is a founding scientist of Athena Neurosciences, now Elan Corporation.Disclosures:Honoraria and Patents received: Elan Corp.Corresponding Author: Dennis J. Selkoe, MD, Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115. 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degeneration via JNK3Aptamers Selected for Recognizing Amyloid β-Protein—A Case for Cautious OptimismDissecting Endoplasmic Reticulum Unfolded Protein Response (UPRER) in Managing Clandestine Modus Operandi of Alzheimer's DiseaseDisaggregation of Aβ42 for Structural and Biochemical StudiesThe influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl‐2/Bax balanceβ-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic ProcessingiPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer's DiseaseFilling the void: a role for exercise-induced BDNF and brain amyloid precursor protein processingLimited activation of the intrinsic apoptotic pathway plays a main role in amyloid-β-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathwaySynthesis and biological evaluation of curcumin analogs as β-amyloid imaging agentsA novel monoclonal antibody against the N-terminus of Aβ1-42 reduces plaques and improves cognition in a mouse model of Alzheimer's diseaseSelf-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide DerivativesAssociation between injury severity and amyloid β protein levels in serum and cerebrospinal fluid in rats with traumatic spinal cord injuryVascular dysfunction-associated with Alzheimer's diseaseEffects of altered RTN3 expression on BACE1 activity and Alzheimer's neuritic pl