Two radioactive tracers enter the same brain, five weeks apart. They are both targeting the same objective: the twisted knots of tau protein that distinguish Alzheimer\u2019s disease from the myriad other conditions that cloud the aging intellect. Same individual, same disease progression, same machine whirring around the skull. Yet, the two scans often disagree, sometimes dramatically, on the presence of tau.<\/p>\n
This disagreement represents the unsettling core of a study released this week in The Lancet, led by a team from the University of Pittsburgh. It indicates that the answer to a crucial question\u2014who possesses Alzheimer\u2019s biology in their brain\u2014may depend on which tracer is administered first.<\/p>\n
The fundamental issue is this: Alzheimer\u2019s exhibits two molecular signatures\u2014adhesive amyloid-\u03b2 plaques, which appear early and often indicate little on their own, and tau tangles, which manifest later and correlate more closely with the progression towards dementia. Detecting tau means identifying the factor that truly predicts decline. \u201cTau is the biology most intimately linked to symptoms and future decline,\u201d states Tharick Pascoal, a behavioral neurologist at Pitt and UPMC who spearheaded the research. To visualize it in a living brain, practitioners employ PET scans and a tracer, a compound that binds to tau and illuminates under the scanner.<\/p>\n
For years, flortaucipir, marketed as Tauvid, has been the standard tracer in clinics throughout the US and Europe. It is effective at identifying tau once the disease has advanced significantly and the tangles have dispersed across the neocortex. However, in the medial temporal lobe, where the issue typically begins, it is less dependable.<\/p>\n
Thus, the Pittsburgh team conducted what they believe to be the largest head-to-head tracer comparison to date. They enrolled 775 individuals across eight locations in the United States and Canada; 682 completed all procedures. Each participant underwent scanning twice, once with flortaucipir and once with a newer investigational tracer named MK6240, the two scans occurring within a 45-day interval to ensure the disease itself had no opportunity to progress in the interim.<\/p>\n
That narrow window was the main objective. \u201cSince participants received both tracer scans within a short time frame, we are examining the same point in the disease trajectory, thus the differences we observe are attributable to the tracers, not temporal alterations,\u201d says Guilherme Povala, a co-lead author.<\/p>\n
The differences proved to be significant. MK6240 excelled at differentiating Alzheimer\u2019s-related impairment from impairment caused by other factors, achieving an area-under-the-curve score of 0.93 compared to flortaucipir\u2019s 0.86, which may seem like a minor difference but is, in reality, substantial. More notably, among individuals exhibiting no cognitive symptoms, MK6240 detected tau in the medial temporal lobe more than twice as frequently: approximately 15 out of every 100 compared to 6. Calculating this reveals that the newer tracer identified 23 additional individuals per 100 as harboring early tau that flortaucipir overlooked. Among those already experiencing memory issues, the disparity persisted in the neocortex as well\u201428 percent positive versus 16, equating to 15 extra mild-impairment cases and 21 additional dementia cases for every hundred scanned. Moreover, MK6240 identified its tau-positive threshold at a considerably lower amyloid burden, a Centiloid value around 53 compared to 81, meaning it detected the tangles earlier during the lengthy, gradual accumulation.<\/p>\n
This does not imply flortaucipir is ineffective. The two tracers broadly illustrated the same framework of tau distribution within the brain, and the older tracer possesses something MK6240 currently lacks: years of post-mortem validation, the diligent process of correlating scans with actual autopsied tissue. Furthermore, flortaucipir is the only tau tracer the FDA has sanctioned for regular clinical use. For the time being, MK6240 resides within research facilities and trials.<\/p>\n
A noteworthy complication also exists. The cohort was 93 percent White, which the authors clearly indicate as a limitation on the generalizability of the findings. Additionally, a more sensitive tracer can be a double-edged sword; detecting tau earlier in an asymptomatic individual is only useful if there are actionable steps available or if the individual desires the knowledge.<\/p>\n
Nevertheless, the implications spread rapidly. Tau PET is increasingly becoming a determinant for new anti-amyloid medications: the donanemab trial, for instance, necessitated a positive tau scan for entry. If the choice of tracer determines who is considered positive, then it subtly influences who qualifies for treatment, who is included in prevention studies, and who is informed of their trajectory towards Alzheimer\u2019s. The study also revealed that MK6240 tended to stage individuals about one Braak.<\/p>\n","protected":false},"excerpt":{"rendered":"
Two radioactive tracers enter the same brain, five weeks apart. They are both targeting the same objective: the twisted knots of tau protein that distinguish Alzheimer\u2019s disease from the myriad other conditions that cloud the aging intellect. Same individual, same disease progression, same machine whirring around the skull. Yet, the two scans often disagree, sometimes […]<\/p>\n","protected":false},"author":1,"featured_media":372812,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"Default","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[179],"class_list":["post-372811","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-source-scienceblog-com"],"_links":{"self":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts\/372811","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=372811"}],"version-history":[{"count":0,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/posts\/372811\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=\/wp\/v2\/media\/372812"}],"wp:attachment":[{"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=372811"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=372811"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wolfscientific.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=372811"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}