Where Has Alzheimer’s Research Taken Us In 2014?

Basic Science Heads In Direction of Early Intervention, Gene Discoveries

2014 was a year of progress for Alzheimer’s research, and the ground that’s been gained is helping us move in promising new directions.

In the January 2015 issue of Lancet Neurology, Randall Bateman, MD, reviews top achievements in Alzheimer’s research in 2014. A long-time colleague of BrightFocus and one of our current grantees, Bateman is the Charles F. and Joanne Knight Distinguished Professor of Neurology at the Washington University of St. Louis Medical School.

BrightFocus is acknowledged as one of many organizations contributing grant funding to Bateman’s research.

Hope Around Early Treatment

There’s been a shift in focus from mid-stage disease to attacking Alzheimer’s as early as possible, even during the decades-long “prodromal” phase of biochemical changes in the brain that happen before Alzheimer’s symptoms become obvious. New monoclonal antibodies under development, like solanezumab, crenezumab, and bapineuzumab, were unsuccessful at improving cognition in established Alzheimer’s, but show promise for people with these early brain changes and/or mild stages of disease. Additional evidence has been gathered in phase 2 and 3 trials of another type of drug which blocks amyloid production, β-secretase inhibitors. So far, results suggest that at the right stage and magnitude of engagement, clinical weapons like these have the potential to “modify”—ie, slow and alter—the course of Alzheimer’s. Early intervention trials “provide tantalizing evidence that these disease-modifying approaches could be nearing confirmation,” Bateman says.

Prevention Focus 

There’s also an effort to target Alzheimer’s disease before it starts in groups who are at high risk. This  strategy is  being investigated in the Dominantly Inherited Alzheimer’ Network Trials Unit (DIAN-TU) trial which Bateman heads; and in the newly-launched Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study led by Harvard researcher and 2010-14 BrightFocus grantee Reisa Sperling, MD; as well as in other investigations.

Advances in Biomarkers, Assessment Tools, Trial Designs.

The need to strike early has brought better tools for screening and early diagnosis of Alzheimer’s, including PET scans, cerebrospinal fluid (CSF) measurements, and better instruments for cognitive assessment. Cognitive assessment—psychological tests that reveal memory and thinking status—is an important way of determining when amyloid accumulations in the brain, such as beta amyloid plaques and tau tangles, may lead to Alzheimer’s symptoms. It’s also a way of determining whether drugs and other therapies are working. And the good news is that “cognitive tests continue to evolve with the development of sensitive measures of cognitive decline associated with amyloid pathology,” Bateman writes. New cognitive “composite” assessment tools and better protocols for assessing cognition repeatedly, over time, promise better metrics to judge whether new drugs and other therapies are working.

Basic Science Advances

The “amyloid pathology in a dish” was developed by Harvard researchers Hoon Choi, PhD, who is a past BrightFocus grantee, and Rudolph E. Tanzi, PhD, a former grantee. This represents a new way of doing research that complements animal models.  Mimicking Alzheimer’s changes in a petri dish makes it possible to study the factors behind gradual amyloid accumulation—and the usefulness of potential new drugs targets—more quickly and efficiently, whereas in live mice, it can take several months for Alzheimer’s pathology to develop to a point where it provides useful research results.

Commenting on this discovery last October, BrightFocus VP of Scientific Affairs Guy Eakin, PhD, said he envisions a time when Alzheimer’s drug development “might begin with a rapid analysis of interactions between a potential compound and beta amyloid, followed by testing in a cell, followed by studies in better animal models, and moving into more streamlined human clinical trials.” Ultimately, “staging” research in this manner, may work to reduce drug development time.

Partnerships and Global Research Networks Collecting and Sharing Data

Shared global research initiatives are advancing collaborative approaches to imaging, treatment, and prevention for Alzheimer's and help ensure that there is enough shared information about targeted groups to assist ongoing, critical discoveries in Alzheimer’s genetics. These collaborative efforts include (to mention a few) the NIH Advanced Medicines Program, which has accelerated implementation of tau PET imaging and RNA analyses; the multi-national Alzheimer’s Disease Neuroimaging Initiative (ADNI) study; the global DIAN registry and other observational cohorts; the European IMI initiatives; and many other cooperative efforts among research institutions and clinical facilities. The most important of these research partners and collaborators are Alzheimer’s patients themselves, who generously share the most intimate details of their illness in order to fight this disease globally.

With hope, news about discoveries from this line of research—and the many others BrightFocus is supporting—lie ahead and will be reported to you in 2015.