Low molecular weight species of tau in Alzheimer's disease are dependent on tau phosphorylation sites but not on delayed post-mortem delay in tissue processing.
Gel electrophoresis and Western blotting of sarkosyl-insoluble fractions enriched in hyper-phosphorylated tau in Alzheimer disease (AD) have been used to analyze the pattern of phospho-tau by using different antibodies directed to the amino-terminal, core and carboxyl terminus of tau, and by using samples with increased artificial post-mortem delay in order to gain understanding on the characteristics of the band pattern and its vulnerability to post-mortem degradation. In addition to the typical profile of three major bands of 68, 64 and 60 kDa, several bands of lower molecular weight have been distinguished in frontal cortex homogenates in four AD cases stage V of Braak and Braak in optimal samples with 2 h of post-mortem delay. Lower bands, ranging from 60 to 22 kDa, are best seen with antibodies directed to the core of tau protein and, particularly, to the carboxy-terminus, thus suggesting the presence of truncated or cleaved forms of tau containing the C-terminal region. This pattern is not the result of post-mortem degradation, as artificial post-mortem delay of the same sample does not reveal the appearance of new bands with time. On the contrary, tau degradation, manifested as a reduction in the number and intensity of the bands, may occur between 8 and 26 h post-mortem and is universal in samples with post-mortem delays of 50h.
Institut Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, 08907 Hospitalet de Llobregat, Spain.
Gabriel
G
Santpere
Berta
B
Puig
Isidre
I
Ferrer
D000544:Alzheimer Disease / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008970:Molecular Weight; D010766:Phosphorylation; D011180:Postmortem Changes; D013048:Specimen Handling; D013997:Time Factors; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D016875:tau Proteins