TAU AND ALZHEIMER’S DISEASE

Abnormal collections of the tau protein accumulate and form tangles, (seen in blue) within neurons, harming
synaptic communication between nerve cells.

Courtesy of NIA

ALZHEIMER’S DISEASE
PROGRESSION AND ASSOCIATED
BIOMARKERS

When misfolded, the proteins Beta-Amyloid and Tau form Plaques and Neurofibrillary Tangles (NFTs), which are the pathologic hallmarks of Alzheimer’s Disease (AD). Amyloid deposition begins well before cognitive signs begin to manifest, but Tau propagation becomes evident shortly before the time that the commonly recognized symptoms of AD first appear.

Adapted from Leuzy, A., Chiotis, K., Lemoine, L. et al. Mol Psychiatry 24, 1112–1134
(2019). https://doi.org/10.1038/s41380-018-0342-8

NEUROIMAGING BIOMARKERS

Positron Emission Tomography (PET) is an advanced imaging modality which provides highly resolved and quantifiable image data based on targeting natural or pathological biochemical processes. It amounts to imaging at the molecular level. PET imaging biomarkers have been developed to assess the presence of amyloid plaques, Tau neurofibrillary tangles (NFTs), and other pathologies, such as neuroinflammation. These pathologies are closely associated with AD. Amyloid imaging has demonstrated its value in selecting subjects who have or are likely to progress to AD. However, as plaque burden is high before a subject is symptomatic, it has not proven valuable as a marker of disease progression. Tau PET imaging holds the promise of enabling AD researchers in Pharma and Academia to follow the progression of neurodegeneratition, and to demonstrate slowing Tau accumulation, and eventually reduction in NFT burden.

MK-6240: A Promising
Next-Generation Tau PET Imaging Biomarker

We have shown that the second generation Tau PET imaging biomarker, MK-6240, is an excellent tool for the evaluation of subjects with suspected AD. It shows good sensitivity and high contrast, as in the adjacent image set. Additionally, it does not exhibit significant non-specific or off-target intracerebral binding, unlike the first generation Tau imaging biomarkers. Off-target binding can confound the assessment of Tau burden, particularly as one images over time to identify changes.

T+A+ Biologically Defined AD

MK-6240 PET images from an amyloid and tau positive subject with biologically defined AD. Also shown are images using AZD4694 (aka NAV4694) is a second generation Aβ PET imaging biomarker, available from Meilieur Technologies.

Courtesy of
Prof. Pedro Rosa-Neto; McGill University

MK-6240 for Tau burden and
progression: A potentially game-changing
addition to the arsenal for assessment of AD

In a recent publication from McGill University, Pedro Rosa-Neto and colleagues have demonstrated that imaging subjects across the spectrum of AD with MK-6240 provides information consistent with Braak staging, the pathological system used to assess the degree of AD at autopsy. For the first time, researchers are provided with MK-6240 as a tool for the active assessment of AD staging, both cross-sectionally and over time, in the living human brain.

Tharick A Pascoal, et al. Brain, awaa180. https://doi.org/10.1093/brain/awaa180