The biochemical parameters of tau pathology

2) the different biochemical signatures observed in AD, PSP, CBD, PiD, MyoD (one to four immunodetected electrophoretic bands); 

As shown in the previous section, a characteristic triplet of electrophoretic bands is detected in AD brain homogenates. A different, but also characteristic pattern, is observed in other diseases with pathological tau and with tau-positive brain lesions (figure 1-B).

Indeed, we demonstrated that pathological tau proteins from progressive supranuclear palsy (PSP) are composed of a main doublet (tau 64, tau 69) (Flament et al. 1991) and a minor tau 74 (Sergeant et al. 1999), while those from Pick' disease are composed of another doublet (tau 60, 64) and a minor tau 69 (Delacourte et al. 1998).

Myotonic dystrophy (MyoD), a familial disease with abnormal CTG repeats on chromosome 19, is characterized by a tau pathology with a major band of 60 kDa. Electrophoretic bands at 64 and 69 are also found, but in lower amounts (Vermersch et al. 1996).

Six main features define tau pathology: 

• 1) the quantitative aspects, using western blots ; 

• 2) the different biochemical signatures observed in AD, PSP, CBD, PiD, MyoD (one to four immunodetected electrophoretic bands); 

• 3) the specific tau isoforms content of brain lesions. Indeed, "disease-specific" sets of tau isoforms aggregate to constitute 4 main categories of tau lesions: class 1: AD (all 6 isoforms), class 2: PSP/CBD (3 Exon10+ isoforms), class 3: PiD (3 Exon10- isoforms) and class 4: MyoD (mainly and sometimes exclusively the shortest tau isoform); 

• 4) the different states of phosphorylation of tau, with hyper and abnormal phosphorylation, as well as disease-specific sites of phosphorylation (ex: ser262); 

• 5) the spatiotemporal progression of tau pathology, which is extremely well correlated with cognitive impairment; 

• 6) the genetic aspects, with pathogenic tau mutations in FTDP-17 or characteristic polymorphisms in PSP. 

References