title: Intraneuronal Aβ accumulation, amyloid plaques, and synapse pathology in Alzheimer's disease.
abstract: BACKGROUND
  β-Amyloid (Aβ) plaques are a pathological hallmark of Alzheimer's disease (AD) and multiple lines of evidence have linked Aβ with AD. However, synapse loss is known as the best pathological correlate of cognitive impairment in AD, and intraneuronal Aβ accumulation has been shown to precede plaque pathology. The progression of Aβ accumulation to synapse loss and plaque formation remains incomplete. The objective is to investigate the progression of intraneuronal Aβ accumulation in the brain.
  
  
  METHODS
  To visualize and analyze the development of Aβ pathology we perform immunohistochemistry and immunofluorescence microscopy using antibodies against different Aβ conformations, synaptic proteins and structural neuronal proteins in brain tissue of AD transgenic mouse models.
  
  
  RESULTS
  Our results show the intraneuronal onset of Aβ42 accumulation in AD mouse brains with aging. We observe an inverse correlation of Aβ and amyloid fibrils with structural proteins within neurites. Images reveal aggregated amyloid within selective pyramidal neurons, neurites and synapses in AD transgenic mice as plaques arise.
  
  
  CONCLUSIONS
  The data support that Aβ42 accumulation and aggregation begin within AD-vulnerable neurons in the brain. Progressive intraneuronal Aβ42 aggregation disrupts the normal cytoarchitecture of neurites.
authors.affiliation: Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA. cae2006@med.cornell.edu
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Capetillo-Zarate
authors.forename: Luis
authors.initials: L
authors.lastname: Gracia
authors.forename: Davide
authors.initials: D
authors.lastname: Tampellini
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Gouras
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000473:pathology*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria