Fig. 6. SERPINA5 is a tau interactor expressed in neurofibrillary tangles and neuritic plaques.

a Cartoon depiction of the lifespan of neurofibrillary tangle maturity ranging from early to advanced forms: pretangle with punctate tau staining, mature tangle with fibrillar tau, and ghost tangle in which only the remnants of the mature tangle remain once the neuron has died. b SERPINA5 accumulates alongside, as well as colocalizes with punctate tau (Tau E178, red) in pretangles. c SERPINA5 accumulates in areas fairly devoid of tau and colocalizes along the fibrillar aspect of tau (Tau E178, red) in mature tangles. d SERPINA5 accumulates in the extracellular space and to a lesser extent colocalizes with tau (Tau pS396, red) in ghost tangles. SERPINA5 is also observed in a subset of dystrophic neurites (arrows, b–d). e Manual quantification of SERPINA5-positive neurofibrillary tangle counts in CA1 region of the posterior hippocampus shows a greater frequency of mature tangles and ghost tangles. Pretangles, mature tangles, and ghost tangles were manually quantified. f, g SEPRINA5 accumulates independently and colocalizes with tau in neuritic plaques as shown by tau (E1) staining and thioflavin-S. Immunofluorescent staining experiments were performed successfully in triplicate for AD and controls. h Immunoblot of tau (E1) using immunoprecipitated SERPINA5 demonstrates a tau-SERPINA5 protein complex in the AD brain, but not in control brain. (Left) Tissue was sampled from frozen hippocampi of a 73-year-old male control (Braak = I, Thal = 0) and an 86-year-old male AD case (Braak = V and Thal = 5). (Right) Tissue was sampled from frozen frontal cortices of a 75-year-old female control (Braak = I, Thal = 0) and a 68-year-old male AD case (Braak = VI and Thal = 5). AD, Alzheimer’s disease; Ctl, control; co-IP, co-immunoprecipitation; Thio-S, thioflavin-S. Note: uncropped western blots can be found in Supplementary Figs. 19 and 20.