ProfilesofADRonaldReagan(1911-2004)
Ronald Reagan (1911-2004) Profiles of AD
Profiles of ADEstimated26.6millionpeopleworldwidesufferedfromAlzheimer'sin2006EstimatesofChinesepatients:6million（2005)and10million(2020),accountsfor1/4oftheworld'sADpatients.AEastWest2510020265-7475-8485+55-64AgegroupFig.2.Age-specificprevalenceofAD,westversuseastChinaNeuroepidemiology2006;27:177-187DOI:10.1159/000096131
• Estimated 26.6 million people worldwide suffered from Alzheimer's in 2006 • Estimates of Chinese patients: 6 million (2005) and 10 million (2020), accounts for 1/4 of the world's AD patients. Profiles of AD
Characteristics of ADPathologicalmanifestations:- Beta-amyloidprecipitation in cerebral cortexand hippocampus一neurofibrillarytangles(神经纤维缠绕，主要为磷酸化神经元微管蛋白一tau蛋白） is mainly phosphorylated neuron tubulin-tau protein.Related mutant genes (account for less than 10% AD cases):-amyloidprecursorprotein (APP),-presenilins 1,2-Apoe4- Two locigavereplicated evidence of association:onewithinCLu(alsocalled APOJ), encoding clusterin or apolipoprotein J, on chromosome 8theother withinCR1, encoding the complement component (3b/4b) receptor1, on chromosome 1 (Nature Genetics volume 41, (2009)
• Pathological manifestations: – Beta-amyloid precipitation in cerebral cortex and hippocampus – neurofibrillary tangles(神经纤维缠绕，主要为磷酸化神经元微管蛋白－tau蛋 白）is mainly phosphorylated neuron tubulin-tau protein. • Related mutant genes (account for less than 10% AD cases): – amyloid precursor protein (APP), – presenilins 1, 2 – Apoe4 – Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (Nature Genetics volume 41, (2009) Characteristics of AD
CharacteristicsofAD-Aβ plaquesHumanAβplaqueNeuNAβPlaqueMergeAPPmice(F,24m)ByLongJG,unpulished
Characteristics of AD -Ab plaques Ab Plaque NeuN Merge APP mice (F,24m) Human Ab plaque By Long JG, unpulished
CellAPPMembraneMoleculeFromAPPtobetaamyloidCelInteriorAPP:Amyloid precursorproteinOSBeta-AmyloidBeta amyloid:Aβ isproduced by thehydrolysis of beta secretase (BACE)andEnzymes- secretase by beta-amyloid proteinBeta-Amyloidprecursor (APP)toform39-42aminoPlaqueacidfragmentsA家National InstituteonAging+
From APP to beta amyloid APP: Amyloid precursor protein Beta amyloid: Aβ is produced by the hydrolysis of beta secretase (BACE) and g- secretase by beta-amyloid protein precursor (APP) to form 39-42 amino acid fragments