Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies.

Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies.

Journal of neurochemistry (2012-08-07)

Connie Luk, Yaroslau Compta, Nadia Magdalinou, Maria José Martí, Geshanthi Hondhamuni, Henrik Zetterberg, Kaj Blennow, Radu Constantinescu, Yolande Pijnenburg, Brit Mollenhauer, Claudia Trenkwalder, John Van Swieten, Wan Zheng Chiu, Barbara Borroni, Ana Cámara, Perdita Cheshire, David R Williams, Andrew J Lees, Rohan de Silva

PMID22862741

ABSTRACT

Characteristic tau isoform composition of the insoluble fibrillar tau inclusions define tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal dementia with parkinsonism linked to chromosome 17/frontotemporal lobar degeneration-tau (FTDP-17/FTLD-tau). Exon 10 splicing mutations in the tau gene, MAPT, in familial FTDP-17 cause elevation of tau isoforms with four microtubule-binding repeat domains (4R-tau) compared to those with three repeats (3R-tau). On the basis of two well-characterised monoclonal antibodies against 3R- and 4R-tau, we developed novel, sensitive immuno-PCR assays for measuring the trace amounts of these isoforms in CSF. This was with the aim of assessing if CSF tau isoform changes reflect the pathological changes in tau isoform homeostasis in the degenerative brain and if these would be relevant for differential clinical diagnosis. Initial analysis of clinical CSF samples of PSP (n = 46), corticobasal syndrome (CBS; n = 22), AD (n = 11), Parkinson's disease with dementia (PDD; n = 16) and 35 controls revealed selective decreases of immunoreactive 4R-tau in CSF of PSP and AD patients compared with controls, and lower 4R-tau levels in AD compared with PDD. These decreases could be related to the disease-specific conformational masking of the RD4-binding epitope because of abnormal folding and/or aggregation of the 4R-tau isoforms in tauopathies or increased sequestration of the 4R-tau isoforms in brain tau pathology.

MATERIALS

Product Number

Brand

Product Description

EP022431005

Eppendorf^® DNA LoBind tubes, capacity 0.5 mL, PCR clean, pkg of 250 ea (5 x 50ea)

EP951032000

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 500 μL, pkg of 40 ea (5 bags × 8 plates)

EP022431021

Eppendorf^® DNA LoBind tubes, capacity 1.5 mL, PCR clean, pkg of 250 ea (5 x 50ea)

EP951031208

Eppendorf^® Deepwell plates, DNA LoBind, 384 wells, white plate, conical bottom, colorless wells, capacity 200 μL, pack of 40 ea (5 bags × 8 plates)

EP951032883

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 1000 μL, pkg of 120 ea (10 bags × 12 plates)

EP951032085

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 500 μL, pkg of 40 ea (5 bags × 8 plates)

EP022431048

Eppendorf^® DNA LoBind tubes, capacity 2.0 mL, PCR clean, pkg of 250 ea (5 x 50ea)

EP951032808

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 1000 μL, pkg of 120 ea (10 bags × 12 plates)

EP951032409

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 500 μL, pkg of 120 ea (10 bags × 12 plates)

EP951033201

Eppendorf^® Deepwell plates, DNA LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 1000 μL, pkg of 80 ea (10 bags × 8 plates)

EP951031607

Eppendorf^® Deepwell plates, DNA LoBind, 384 wells, white plate, conical bottom, colorless wells, capacity 200 μL, pack of 120 ea (10 bags × 12 plates)

EP951040601

Eppendorf^® Protein LoBind Microplate 384/V-PP, PCR clean, V-bottom clear wells, white border, pack of 240 ea (10 bags × 24 plates)

EP951032123

Eppendorf^® Deepwell plates, Protein LoBind, 96 wells, yellow plate, conical bottom, colorless wells, capacity 500 μL, pkg of 40 ea (5 bags × 8 plates)

EP951032921

Eppendorf^® Deepwell plates, Protein LoBind, 96 wells, yellow plate, conical bottom, colorless wells, capacity 500 μL, pkg of 20 ea (5 bags × 4 plates)

EP951033308

Eppendorf^® Deepwell plates, Protein LoBind, 96 wells, white plate, conical bottom, colorless wells, capacity 500 μL, pkg of 80 ea (10 bags × 8 plates)

EP022431064

Eppendorf^® Protein LoBind tubes, capacity 0.5 mL, PCR clean, pkg of 100 ea (2 x 50ea)

EP022431081

Eppendorf^® Protein LoBind tubes, capacity 1.5 mL, PCR clean, pkg of 100 ea (2 x 50ea)

EP022431102

Eppendorf^® Protein LoBind tubes, capacity 2.0 mL, PCR clean, pkg of 100 ea (2 x 50ea)