Colocalization of tau and alpha-synuclein epitopes in Lewy bodies.
The major protein constituent of Lewy bodies (LBs), the pathological hallmark of Parkinson disease and dementia with Lewy bodies, is considered to be alpha-synuclein, but other proteins, in particular the microtubule-associated protein tau, have been implicated in the pathogenesis of LBs. Tau is the major structural component of neurofibrillary tangles (NFTs). Both direct immunochemical studies of partially purified LBs and indirect immunohistochemical studies have suggested that LBs may contain tau, but most of these studies were based upon a single tau antibody, and immunologic cross-reactivity was not completely excluded. To gain insight into the relation between tau and alpha-synuclein in LBs, double immunostaining was performed in Lewy body cases with a rabbit polyclonal antibody to alpha-synuclein and a panel of monoclonal antibodies to phospho- and nonphospho-tau epitopes (Alz50, CP9, CP13, PG5, TG3, PHFI) that spanned the length of the tau molecule. Tau-immunoreactive LBs were present in the medulla in 80% of the cases, irrespective of Braak stage. All tau antibodies recognized at least some LBs, arguing against nonspecific antibody cross-reactivity. In most lesions the tau immunostaining was present at the periphery of the LB. The phospho-tau antibody, TG3, detected more LBs than any of the other tau antibodies. The proportion of LBs with tau immunoreactivity was greatest in neurons vulnerable to NETs, such as those in the locus ceruleus and basal nucleus of Meynert, and least in neurons resistant to NFTs, such as the dorsal motor nucleus of the vagus in the medulla. The present results suggest that tau may coaggregate with alpha-synuclein in LBs, especially in neuronal populations vulnerable to both NFTs and LBs.
Ishizawa
Takashi
T
Department of Pathology (Neuropathology), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Mattila
Petri
P
Davies
Peter
P
Wang
Dengshun
D
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D020532:Basal Nucleus of Meynert / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism* / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
D000939:Epitopes; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins