OBJECTIVE: Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting of beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal by microglia. Here, we investigate whether naturally occurring autoantibodies to beta-amyloid contribute to beta-amyloid plaque removal in nonimmunized AD patients. METHODS: We generated an AD tissue microarray with 2,325 tissue specimens from 3 defined central nervous system regions of 48 AD patients and 48 age-matched control patients. Absolute quantification of beta-amyloid, beta-amyloid plaque-bound IgG, and phagocytic, resting, and activated microglia and microhemorrhages was done using a standardized, highly reproducible scoring system. RESULTS: The majority of neuritic plaques are decorated by IgG. AD patients with prominently IgG-labeled neuritic plaques have a significantly reduced plaque burden and an increase in phagocytic microglia, yet no increase in microhemorrhages. INTERPRETATION: Autoantibodies directed against beta-amyloid are common in AD patients and may contribute in controlling plaque burden.
OBJECTIVE: Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting of beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal by microglia. Here, we investigate whether naturally occurring autoantibodies to beta-amyloid contribute to beta-amyloid plaque removal in nonimmunized ADpatients. METHODS: We generated an AD tissue microarray with 2,325 tissue specimens from 3 defined central nervous system regions of 48 ADpatients and 48 age-matched control patients. Absolute quantification of beta-amyloid, beta-amyloid plaque-bound IgG, and phagocytic, resting, and activated microglia and microhemorrhages was done using a standardized, highly reproducible scoring system. RESULTS: The majority of neuritic plaques are decorated by IgG. ADpatients with prominently IgG-labeled neuritic plaques have a significantly reduced plaque burden and an increase in phagocytic microglia, yet no increase in microhemorrhages. INTERPRETATION: Autoantibodies directed against beta-amyloid are common in ADpatients and may contribute in controlling plaque burden.
Authors: Yona Levites; Brian O'Nuallain; Rama Devudu Puligedda; Tomas Ondrejcak; Sharad P Adekar; Cindy Chen; Pedro E Cruz; Awilda M Rosario; Sallie Macy; Alexandra J Mably; Dominic M Walsh; Ruben Vidal; Alan Solomon; Daniel Brown; Michael J Rowan; Todd E Golde; Scott K Dessain Journal: J Neurosci Date: 2015-04-22 Impact factor: 6.167
Authors: Carsten Friedrich; André O von Bueren; Larissa Kolevatova; Christian Bernreuther; Tobias Grob; Diego Sepulveda-Falla; Leander van den Boom; Manfred Westphal; Ronald Simon; Markus Glatzel Journal: Childs Nerv Syst Date: 2015-12-21 Impact factor: 1.475
Authors: Richard Dodel; Frauke Neff; Carmen Noelker; Refik Pul; Yansheng Du; Michael Bacher; Wolfgang Oertel Journal: Drugs Date: 2010-03-26 Impact factor: 9.546