RESEARCH. Alzheimer’s disease is a protracted process. It can take 15 years or more from the first molecular signs indicating that something has changed in the brain until dementia symptoms occur. Silke Kern, who recently was appointed to a high clinical ALF medical position, is examining what’s happening in the brain from the earliest changes that can be measured in cerebrospinal fluid until the patient later develops dementia.
The world’s population is aging, which means that the number of persons with dementia will greatly increase. In 2050 it’s estimated that the number of people with dementia will have more than tripled, from 40 million today to 140 million. Alzheimer’s disease, the most common form of dementia, is characterized by beta-amyloid plaques and degeneration of synapses and neurons.
“It’s well known that Alzheimer’s disease starts many years before the patient is affected by cognitive symptoms,” Silke Kern says. “It would be great if we also knew more exactly what kind of mechanisms cause the early Alzheimer’s processes to accelerate and become fully developed Alzheimer’s dementia, because then maybe it would also be possible to find ways to slow down the process.”
Based on the H70 study
Recently Silke was appointed to a high clinical ALF medical position to be able to carry out her project, which is a longitudinal study of the earliest signs of Alzheimer’s disease and its development during the years that follow. The project is based on the H70 study, a population study in which large groups of 70-year-olds are examined with extensive physical and psychological examinations. Participants of the study are examined with brain magnetic resonance imaging (MRI) as well, and many of the study participants also agree to undergo a lumbar puncture to extract cerebrospinal fluid:
“It doesn’t hurt as long as the person taking the sample is experienced. It feels about the same as giving a blood sample,” Silke says.
She personally has collected all the spinal fluid samples for the latest cohort of 70-year-olds, and starting next year, she will begin collecting follow-up samples for study participants who are turning 75.
The study measures biomarkers in the spinal fluid that the world leading researchers in clinical neurochemistry Professor Kaj Blennow and Professor Henrik Zetterberg in Mölndal have found correspond very well with the development of Alzheimer’s disease. The biomarkers are Amyloid Beta 42, the levels of which would be lower than usual, as well as T-tau and P-tau, the levels of which would be elevated.
“These biomarkers are very reliable and clearly linked to Alzheimer’s disease. But what’s puzzling is that there are people who have these signs in their spinal fluid, but who never develop dementia. They remain clinically healthy, in other words, and we don’t know why this is so,” says Silke.
The project also encompasses more proteins that are promising biomarkers for degeneration of the brain’s synapses.
Combining biomarkers in spinal fluid with brain imaging
There is still much that is not known when it comes to Alzheimer’s disease. For example, researchers are not in complete agreement about whether the plaques that form in the brain from the accumulation of beta-amyloid are the cause of the disease, or whether these plaques are another sign of the process that causes the degeneration of neurons and synapses. It’s clear that the process that drives the development of the disease is complex.
A current hypothesis is that impaired blood flow in the brain plays an important role in the development of Alzheimer’s disease. Previous research has shown that between 20 and 40 percent of all people with mild cognitive impairment, a precursor to dementia, have cerebral microbleeds. Therefore, in collaboration with researchers who are experts in brain imaging, Silke Kern’s project will correlate changes in the brain white matter and signs of cerebral microbleeds with the process that causes neurons and synapses to atrophy.
“At present there’s no other population study that has examined the intricate relationship between the two different aspects of the disease process in Alzheimer’s disease. Here we are combining degeneration markers of synapses and neurons with the brain’s blood supply,” says Silke.
A doctor with dual specialties
Silke Kern received her medical degree at the University of Würzburg, which is a highly respected, old university in Bavaria in southern Germany. She obtained her doctorate in parallel with her medical studies and defended her doctoral thesis immediately after receiving her degree with an experimental dissertation within cardiology, where she investigated the creatine kinase system in mouse hearts.
“It was tough to finish my studies while working on my dissertation. There were many late nights and a lot of weekend work. But I always knew I wanted to defend my thesis and I was very interested in research,” recalls Silke, who did her internship after medical school in Würzburg and then specialized in neurology.
As a resident physician (ST-läkare), she had the opportunity to carry out her specialty training in adjacent areas. Because she liked Sweden and had heard of the research in aging in psychiatry here, she contacted Ingmar Skoog.
“From a research standpoint, that was the best thing that could have happened to me! Ingmar Skoog, Kaj Blennow and Henrik Zetterberg are fantastic mentors. They bring me along to scientific congresses, they introduce me to leading researchers, and they let me work with interesting research papers and research projects. All three have been a great support to me in my research career,” says Silke, who also would like to thank her clinical director, Johan Sandelin, and Professor Margda Waern for the support she has received from them.
When she had finished her specialist residency training, she remained at Sahlgrenska University Hospital, where she also chose to specialize in psychiatry, and consequently she now has dual specialties. And soon she can celebrate her tenth anniversary as a physician and researcher at the Memory Clinic:
“I love living in Sweden, and I love my job!” she declares.
TEXT AND PHOTO: ELIN LINDSTRÖM CLAESSEN