Webinar from the Association for Frontotemporal Degeneration featuring the Penn FTD Center's co-directors, Dr. Lauren Massimo and Dr. David Irwin:
AFTD Webinar – Brain Donations: Who, What, Where, When, and Why?
Brain donation is a deeply meaningful contribution to research for FTD and related disorders. The gift of brain donation is critical to advance the science of FTD research and accelerate the discovery of new diagnostics and mechanisms of disease needed to develop treatment trials to slow or stop FTD and related disorders.
A key obstacle to the development of new therapeutics for FTD and related disorders is the difficulty in diagnosing the specific biological cause of patient symptoms in living patients. Moreover, there are often delays in an accurate diagnosis. Indeed, diagnosis of FTD and related conditions is not absolutely certain without neuropathological examination of the brain after a patient’s passing. There are several microscopic causes of FTD and related disorders that relate to the abnormal accumulation of different type of proteins in brain cells that contribute to neurodegeneration and patient symptoms. These proteins are normally functioning in healthy adult brains, but in FTD and related disorders they can misfold and disrupt brain cell functioning to cause disease.
The two main causes of FTD are frontotemporal degeneration with accumulation of the protein tau (FTLD-Tau) or the protein TDP-43 (FTLD-TDP). These different proteins have very different functions in the brain; tau is a protein that supports brain cell structure while TDP-43 is a protein that regulates gene expression (i.e. the function of cells). Thus, treatment strategies for these very different protein mechanisms will be different, necessitating an accurate and early diagnosis to differentiate these diseases. Currently in patients without a genetic cause of FTD or related disorder we cannot tell these two different diseases apart, as they can have similar clinical features of FTD during life and affect similar parts of the brain. Please see the figure below showing how different FTLD-Tau and FTLD-TDP microscopic disease can cause the same FTD symptoms.
An analogy to this problem is seen in cancer, where different types of tumors can affect the liver or lung and cause similar symptoms but have different biological causes and thus, different treatment strategies. In cancer, we can easily obtain a biopsy with minimal risk and examine the tumor under the microscope to develop a new therapy. With FTD and related disorders we cannot safely obtain brain tissue by biopsy during life. Thus, we need research to advance our ability to detect these pathologies with other methods, such as imaging of the brain, blood, spinal fluid or other new tests that detect these specific pathologies which we call “biomarkers.”
Brain Donation FAQ
How does brain donation help science? Brain donation is critical to develop new tests (biomarkers) that can tell us if FTLD-Tau, FTLD-TDP, Alzheimer’s disease or related microscopic pathologies are causing the symptoms in a living patient. Biomarkers that reflect the specific disease processes in the brain can also be used to track disease progression to give patients and families important prognostic information for what to expect on rate of progression of symptoms and be used in a clinical trial as a measure of how a new drug is affecting the underlying biology of FTD and related disorders. The final diagnosis of FTLD-Tau, FTLD-TDP or Alzheimer’s disease from neuropathological examination from brain donation is critical to inform the research data collected during life for Penn to develop new biomarker tests to improve diagnosis. Moreover, the tissue can be directly analyzed to develop new tests and better understand the mechanisms of disease to guide the development of new treatments. At Penn we perform NIH funded research and share de-identified tissue and data broadly with the scientific community so that as a team the FTD research community can advance discoveries. Thus, brain donation is a deeply meaningful contribution to science that is urgently needed to advance the care for FTD and related disorders.
How does brain donation help my family? The final diagnosis of the neuropathological cause of a patient’s symptoms can be a source of closure and healing for families. The delay in diagnosis for FTD and related disorders is on average three years or more from the onset of symptoms and the diagnostic journey can unfortunately involve multiple medical visits over years before the progression of disease is clear for a health care professional to make a diagnosis of FTD or related condition. Uncertain diagnosis can be a major stressor for families and a final neuropathological diagnosis can provide a final answer to the cause of a loved one’s symptoms. In addition, the neuropathological diagnosis, in addition to genetic counselling, has potential to improve the understanding of family risk for FTD and related disorders. There is an important distinction between brain donation and brain autopsy. Brain donation is an extremely meaningful gift of brain tissue to researchers who study FTD and related disorders to advance the science of FTD. Brain autopsy is a clinical procedure where the brain is examined by a neuropathologist to perform a diagnostic evaluation of the brain to formulate a final diagnosis. At Penn and most research programs, a clinical evaluation and report is generated by a neuropathologist and shared with patient families as part of the process of brain donation. This final report is reviewed with patient families by the treating clinician at the Penn FTDC to answer questions and review the findings. Thus, at Penn brain donation also includes a final clinical report of the findings to patient families.
How do I participate in brain donation at Penn? Brain donation is a precious gift to research that is incredibly valued by our team. We currently have research funding to collect brain tissue from patients with FTD and other specific related disorders who participated in research during life. If you are interested in participating in a clinical research program at Penn please see the research section of our website for a list of our ongoing studies and contact information below.
Logistical considerations for brain donation It is helpful to make decisions for brain donation early and include your loved one with FTD or a related disorder in the discussion to help make the best decision for your family. It also can be helpful to discuss with close family, friends or your primary care doctor. At Penn, we provide an information packet about the logistics and contact information for the brain donation program when patients are interested in participating. It is helpful to have this contact information and logistics for coordination of the donation process early, so you have plenty of time to prepare and have the information ready to contact the program near the time of death. The final consent for brain donation occurs after the time of passing by the next-of-kin. At Penn the treating clinician or close colleague at Penn will call to obtain the final consent by phone, review logistics and answer questions. Once consent is obtained the funeral home and brain donation program move forward with transportation of the body to obtain the brain tissue at Penn. The research program covers the costs for transportation for brain donation and the process of obtaining brain tissue is compatible with most funeral practices. A final report of the neuropathological diagnosis is provided by the neuropathologist and sent to the next-of-kin who consented for the brain donation. This process can take several months for the neuropathologist to carefully process the tissue into microscope slides, review them in detail, and generate a formal report. You can always check in with your clinical team at the Penn FTDC with questions and updates. Once the report is sent to you, your treating clinician at the Penn FTDC will contact you to review the findings in the report and answer questions. The neuropathological diagnosis for patients in the research program who participated in brain donation is used to inform all of the clinical data collected during life for ongoing studies that examine the relationship between clinical symptoms, blood and spinal fluid markers, imaging and genetics with the neuropathology. Moreover, the brain tissue is used for various projects at Penn and beyond to discover new diagnostics and treatment targets. Thus, there is a large impact of brain donation on advancing the science of FTD and related disorders and the implication for improving clinical care is far reaching.
How do I learn more about research updates from brain donation? Research in FTD is a partnership between patients, families and scientists. At the Penn FTDC we share feedback on our discoveries with patients and families in two annual patient and caregiver outreach events. We also have a quarterly newsletter where we share updates of what we learn from our ongoing studies. Please see our media section to access videos of our previous events to learn more about the advances we have made from clinical research at Penn.