With the approval of novel antibody therapies such as Leqembi and Kisunla, Alzheimer's research is experiencing a turning point. Lindsay Hohsfield is a neuroimmunologist, APART-USA fellow at the Austrian Academy of Sciences, and is researching the molecular mechanisms of the disease as well as strategies for early detection and prevention.

Antibody-therapies and blood-based biomarkers

Could you provide an overview of the recent breakthroughs in Alzheimer’s research?

Lindsay Hohsfield: The most significant recent breakthrough for the field of Alzheimer’s disease has been the regulatory approval (in the US this is the FDA and, in the EU, the European Commission) of Leqembi (lecanemab) and Kisunla (donanemab), which are antibody therapies that target amyloid plaques in the brain. Clinical trials have now shown that these therapies are not only very effective in removing Abeta from the brain (one of two toxic proteins that accumulate in the Alzheimer’s brain), but also in slowing cognitive decline in patients with early-stage Alzheimer’s disease.

But also: Blood-based biomarkers are transforming Alzheimer’s diagnosis by replacing costly and invasive methods like PET scans or spinal taps with simple, accessible blood tests. Multi-omics approaches allow researchers to study thousands of molecular interactions simultaneously, revealing how genes, proteins, and cells change with disease. Artificial intelligence further accelerates progress by analyzing massive datasets and screening potential drug compounds much faster than humans could.

Clinical trials have now shown that these treatments slow cognitive decline by 27-35%.

How are new therapies, such as Leqembi (Lecanemab) and Donanemab (Kisunla), changing the treatment of early-stage Alzheimer’s?

Hohsfield: Leqembi (lecanemab) and Kisunla (donanemab) are transforming early-stage Alzheimer’s disease treatment. Clinical trials have now shown that these treatments slow cognitive decline by 27-35%, meaning if taken early enough, we now have treatments that can significantly slow disease progression – ultimately resulting in more years without disability or cognitive impairment, more time with family, and more memories for people with early-stage Alzheimer’s disease.

What are the biggest challenges researchers face when developing therapies for Alzheimer’s disease?

Hohsfield: One of the biggest challenges that researchers face when developing therapies for Alzheimer’s disease is the blood-brain barrier. The blood-brain barrier or BBB is a protective barrier between the brain and the rest of the body, meaning it tightly controls what is allowed in and out of the brain. While this is crucial for protecting the brain against harmful molecules, it means that researchers have an extremely difficult time trying to transport therapies across this barrier and into the brain. However, there are several innovative strategies under development to overcome this barrier, including a molecular “Trojan-horse” that helps molecules get across the BBB.

Several genetic factors have been identified that increase a person’s risk for Alzheimer’s.

What role do genetic factors and lifestyle play in the risk, progression, and prevention of Alzheimer’s?

Hohsfield: Several genetic factors have been identified that increase a person’s risk for Alzheimer’s. For late onset sporadic Alzheimer’s disease, the strongest genetic factor is APOE4. People with one copy of APOE4 have approximately 3-4 times higher risk of developing Alzheimer's disease, and people with two copies of APOE4 have 8-15 times increased risk of developing Alzheimer's disease. APOE4 carriers show greater amyloid accumulation and faster rates of cognitive decline. APOE4 carriers also may respond differently to amyloid-targeting therapies, including having higher rates of brain swelling.

What is familial Alzheimer’s disease, and when might genetic testing be useful?

Hohsfield: Familial Alzheimer’s disease (FAD) is a rare inherited form caused by mutations in the APP, PSEN1, or PSEN2 genes. It usually appears between ages 30 and 50, and each child of an affected person has a 50% chance of inheriting the mutation, often impacting multiple generations. 

Genetic testing is recommended only for families with a strong history of early-onset Alzheimer’s (across three or more generations) and can help guide decisions about research, finances, and family planning.

How do you envision Alzheimer’s therapy in 20 years?

Hohsfield: In 20 years, I envision routine blood-based amyloid screening for those at genetic risk, with early treatment preventing or delaying Alzheimer’s—potentially pushing onset from age 55 to 90 or avoiding it altogether.

In 20 years, I envision a broad range of therapies targeting tau, neuroinflammation, and neuronal loss, enabling personalized, combination treatments that match each patient’s disease stage and biology—transforming Alzheimer’s into a preventable and manageable condition.

What do you find interesting about the research landscape in Austria, and why did you decide to come here?

Hohsfield: I joined the Medical University of Innsbruck to explore neuroimmunology, a field challenging the outdated notion that the brain exists in immune isolation—my recent research identifying novel pathways for immune cell brain entry exemplifies the critical neuroimmune interactions underlying neurological diseases. From the outset, I believed that understanding this brain-immune dialogue holds the key to developing transformative immunotherapies for neurological conditions.

My tenure at MUI provided an exceptional foundation in neuroimmunology while fostering invaluable collaborations with brilliant colleagues who seamlessly integrate cutting-edge research with compassionate patient care—the institution's unique strength lies in its people who balance scientific excellence with translational impact.

Arriving in 2010 as a Fulbright scholar, I completed my PhD in Neuroscience while learning German, meeting my future husband, and developing a profound connection to Austria that made my return as an APART-US fellow deeply meaningful. This role enables me to bridge Austrian, European, and American research networks—essential for combating a global disease that transcends borders, a vision I've extended through founding Youngtimers, a nonprofit supporting early-onset Alzheimer's patients. I'm excited to expand our European partnerships and strengthen the international coalition of scientists, clinicians, and advocates working toward our shared mission of serving patients and families worldwide.