Alzheimer`s: Amyloid and tau are a perilous couple
Current findings give backing to Anti-Amyloid Therapies

Date:
March 30, 2022
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
In the course of Alzheimer's disease, two proteins called 'amyloid'
and 'tau' accumulate in the brain. A new study with more than 200
participants now provides insights into the interaction of these
pathological phenomena. The data suggest that tau load in the
brain impairs memory functions only when amyloid burden is also
high. These findings therefore support therapeutic approaches
aimed at removing amyloid from the brain in the early stages of
Alzheimer's disease.



FULL STORY ==========================================================================
In the course of Alzheimer's disease, two proteins called "amyloid"
and "tau" accumulate in the brain. A DZNE study with more than 200
participants now provides insights into the interaction of these
pathological phenomena. The data suggest that tau load in the brain
impairs memory functions only when amyloid burden is also high. These
findings therefore support therapeutic approaches aimed at removing
amyloid from the brain in the early stages of Alzheimer's disease. A
research team led by Prof. Emrah Du"zel reports on this in the journal
Brain.


==========================================================================
"It has long been known that deposits of tau proteins in the so-called hippocampus and in neighboring brain areas impair memory. In the case of amyloid, on the other hand, no clear relationship to memory performance
has been found to date. For this reason, among others, it is debated
whether it makes sense at all to target amyloid therapeutically. Our
current results suggest that this could indeed be helpful for memory
function in the early stages of the disease," says brain researcher Emrah Du"zel, speaker of the DZNE's Magdeburg site and director of the Institute
of Cognitive Neurology and Dementia Research of Otto-von-Guericke
University Magdeburg. "The crucial aspect is that you don't look at
tau in isolation, but together with amyloid pathology. This is where
a link becomes apparent when you study a larger number of individuals
and accordingly have solid statistics." Data Acquisition at Several
Sites The data now evaluated come from a DZNE long-term study (DELCODE)
in collaboration with university hospitals in which ten study centers
across Germany are participating. The current investigations included
data from 235 subjects over 60 years of age. This group included not only cognitively normal adults, but also individuals with memory problems that
were either mild ("mild cognitive impairment") or only subjectively
perceived -- i.e. common testing methods could not detect memory
impairment. Data from individuals with dementia were not considered,
because the focus was on early stages of Alzheimer's disease. Du"zel's
team analyzed the cerebrospinal fluid (CSF) of the study subjects and
examined their memory and brain activity using functional magnetic
resonance imaging (fMRI).

Levels of amyloid and tau proteins in CSF are commonly used indicators for assessing the burden of these proteins on the brain. Since amyloid and
tau proteins also occur in the CSF of cognitively healthy individuals,
the study participants were grouped according to established thresholds
into those with pathological, i. e. abnormal readings, and those with
levels in the normal range. To assess memory by fMRI, study participants
were given the task of memorizing photographic images while brain activity
in the hippocampus -- the switchboard for memory -- was simultaneously registered. "Using this task fMRI, we found that hippocampal activation
to new images decreased with increasing tau load, and so did memory performance, only when amyloid load was high. In other words, high
load by both proteins was the likely cause of memory impairment,"
Du"zel says. "This relationship has not been demonstrated in previous
studies. The necessary technical harmonization across all study sites is
very complex. Such studies require the kind of infrastructure that DZNE
has established over the years." Backing for Anti-Amyloid Therapies
"Our data show several relevant associations. If amyloid levels are
beyond the pathological threshold, and only then, we see that the
higher the tau levels in the CSF, the worse the memory performance and
the more pronounced the reduction in hippocampal activation," Du"zel
continues. "And we also see that if you compare study participants with
similar tau data, memory performance is more impaired in those with
abnormal amyloid levels than in those with amyloid levels in the normal
range." The causes of the interaction of amyloid and tau pathology are
still largely unclear, Du"zel acknowledges, but concludes: "Our data
show that it might be useful to reduce tau load if amyloid burden is
also high. However, our findings also suggest that it might help to
reduce or keep amyloid burden low in the early stages of the disease,
even if tau load remains the same. One can infer from our results that
memory could benefit from this." This is where anti-amyloid therapies
using "monoclonal antibodies" come in that are currently undergoing
clinical trials and of which the drug "Aducanumab" (brand name: Aduhelm)
is the first to have been approved in the USA. However, the approval is controversial. Du"zel: "Regardless of how well this particular drug is clinically effective, our study results provide additional support for
the general concept of targeting amyloid. This approach should continue
to be considered in therapy development."

========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Emrah Du"zel, Gabriel Ziegler, David Berron, Anne Maass, Hartmut
Schu"tze, Arturo Cardenas-Blanco, Wenzel Glanz, Coraline Metzger,
Laura Dobisch, Martin Reuter, Annika Spottke, Frederic Brosseron,
Klaus Fliessbach, Michael T Heneka, Christoph Laske, Oliver Peters,
Josef Priller, Eike Jakob Spruth, Alfredo Ramirez, Oliver Speck,
Anja Schneider, Stefan Teipel, Ingo Kilimann, Wiltfang Jens,
Bjo"rn-Hendrik Schott, Lukas Preis, Daria Gref, Franziska Maier,
Matthias H Munk, Nina Roy, Tomasso Ballarini, Renat Yakupov,
John Dylan Haynes, Peter Dechent, Klaus Scheffler, Michael Wagner,
Frank Jessen. Amyloid pathology but not APOE e4 status is permissive
for tau-related hippocampal dysfunction.

Brain, 2022; DOI: 10.1093/brain/awab405 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220330103319.htm

--- up 4 weeks, 2 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)