We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us

Roche Diagnostics

Develops, manufactures, and markets a wide range of in vitro diagnostic systems, instruments, reagents, and tests read more Featured Products: More products

Download Mobile App


ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Caspase-6-Cleaved Tau Is Relevant in Alzheimer's Disease

By LabMedica International staff writers
Posted on 27 Jun 2022
Print article
Image: Neuronal marker positivity in the middle frontal and inferior temporal gyrus of human post-mortem brains with common tauopathies (Photo courtesy of University of California San Francisco)
Image: Neuronal marker positivity in the middle frontal and inferior temporal gyrus of human post-mortem brains with common tauopathies (Photo courtesy of University of California San Francisco)

Alzheimer’s disease (AD) is characterized by the formation of aggregates of the tau protein in brain cells called neurofibrillary tangles. Although deposits of the amyloid β-protein are also found in AD brains, some scientists think that the tau protein aggregates are primarily responsible for the development of AD.

Proteolytic truncation of tau (tr-tau) by active caspases has recently been recognized as a significant contributor to tau-driven nosology in AD and primary tauopathies. Caspases (Casps), cysteine-aspartic proteases, are proteolytic enzymes with well-defined roles in apoptosis and inflammation that cleave their substrates after specific aspartic acid (D) residues.

A team of Neuroscientists at the University of California San Francisco (San Francisco, CA, USA) and their colleagues used post-mortem brain samples from individuals with AD, Pick’s disease (PiD) which is a 3R tauopathy and 4R tauopathies: corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and argyrophilic grain disease (AGD). They generated two neoepitope monoclonal antibodies against tr-tau sites (D402 and D13) targeted by active Casp-6 (aCasp-6). Then, they used five-plex immunofluorescence to quantify the neuronal and astroglial burden of aCasp-6, tr-tau, p-tau and their co-occurrence in healthy controls, AD and primary tauopathies.

The team also performed immunofluorescence (IF) assays on eight μm thick tissue sections from paraffin-embedded tissue blocks of the middle frontal gyrus and inferior temporal gyrus. Each single slide underwent immunohistochemical detection for up to five antibodies to detect: neurons (NeuN), p-tau (CP13/PHF-1), aCasp-6 and Casp-6-tr-tau. Multiplex IF was performed on a Ventana discovery ultra-automated staining instrument (Roche Diagnostics, Indianapolis, IN, USA) with antibodies that were previously characterized in single labeled immunostaining. Cell quantification was performed using a Zeiss AxioImager A2 microscope equipped with a Zeiss Colibri 7 (Carl Zeiss Microscopy, Oberkochen, Germany).

The scientists reported that that the number of brain cells expressing activated caspase-6 and the truncated tau fragments was considerably higher in AD and PiD than in 4R-tauopathies, such as PSP and CBD. Notably, these truncated tau fragments can be detected in the cerebrospinal fluid. Thus, these truncated tau proteins could serve as biomarkers for AD and PiD diagnosis and help distinguish individuals with AD and Pick’s disease from those with 4R-tauopathies. Although the levels of phosphorylated tau differed among the AD and other tauopathies, the magnitude of differences in truncated tau levels was more profound. The study suggests that the truncated tau fragments could serve as more sensitive biomarkers than phosphorylated tau.

Lea T. Grinberg, MD, PhD, a Professor of Neurology and co-senior author of the study, said, “Our results suggest that when we measure phosphorylated tau as a proxy of tau pathology in AD, we are missing almost half of the story. Any in vivo measure using phosphorylated tau only to monitor AD (progression and clinical trial results) is missing a lot. Furthermore, we are not detecting well which class of neurons are the most vulnerable, so we cannot create the right strategies to protect them. Importantly, caspase-6 inhibitors are available and experimental work shows that inhibiting caspase-6 activation decreases tau pathology. Thus, caspase-6 inhibitors could be an effective therapy for AD.”

The authors concluded that early modulation of active Casp-6 to reduce tr-tau pathology is a promising therapeutic strategy for AD and PiD, but is unlikely to benefit 4R tauopathies. The large percentage of tr-tau-positive neurons lacking p-tau suggests that many vulnerable neurons to tau pathology go undetected when using conventional p-tau antibodies. The study was published on May 4, 2022 in the journal Neuropathology and Applied Neurobiology.

Related Links:
University of California San Francisco 
Roche Diagnostics 
Carl Zeiss Microscopy 

Gold Supplier
COVID-19 Antigen Self-Test
Panbio COVID-19 Antigen Self-Test
Lab Incubator
Fecal Occult Blood Test
iFOB Assay
Urine Test Strip
HealthMate DA-7

Print article


Clinical Chem.

view channel
Image: ELISA kit for liver-type fatty acid–binding protein (L-FABP). The level of L-FABP present in urine reflects the level of renal tubular dysfunction (Photo courtesy of Sekisui Medical Co)

Urinary Biomarkers Predict Weaning From Acute Dialysis Therapy

Acute kidney injury is associated with a higher risk of chronic kidney disease (CKD), end-stage renal disease, and long-term adverse cardiovascular effects. Critically ill patients with acute kidney injury... Read more


view channel
Image: Ring-form trophozoites of Plasmodium vivax in a thin blood smear (Photo courtesy of Centers for Disease Control and Prevention)

Immune Regulators Predict Severity of Plasmodium vivax Malaria

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules... Read more


view channel
Image: Breast cancer spread uncovered by new molecular microscopy (Photo courtesy of Wellcome Sanger Institute)

New Molecular Microscopy Tool Uncovers Breast Cancer Spread

Breast cancer commonly starts when cells start to grow uncontrollably, often due to mutations in the cells. Overtime the tumor becomes a patchwork of cells, called cancer clones, each with different mutations.... Read more


view channel
Image: With Cell IDx’s acquisition, Leica Biosystems will be moving its multiplexing menu forward (Photo courtesy of Leica Biosystems)

Leica Biosystems Acquires Cell IDx, Expanding Offerings in Multiplexed Tissue Profiling

Leica Biosystems, a technology leader in automated staining and brightfield and fluorescent imaging (Nussloch, Germany), has acquired Cell IDx, Inc. (San Diego, CA, USA), which provides multiplex staining... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.