Here, we discuss novel insights into FTD-related diseases made possible through the analysis of patient data from the Brain Bank.

Recent research at the FTD Center by cognitive neurologist Dr. David Irwin sheds light on Pick disease, one cause of frontotemporal degeneration (FTD) syndromes.

Pick disease is named for Dr. Arnold Pick, who discovered the disease in 1892 by examining the brains of patients who showed progressive language difficulty and behavioral changes during the later stages of life. We would now call this FTD. Pick noticed that only particular regions of the brain in the frontal and temporal lobes showed atrophy, or loss of tissue. Later, Dr. Alois Alzheimer found distinctive round clumps of protein in frontal and temporal lobe brain cells in patients similar to those Dr. Pick described, and called these “Pick bodies” in honor of Dr. Pick. Since these initial findings, we heave learned much more about FTD and Pick disease.

We now know that Pick bodies are composed of a misfolded protein called ‘tau,’ and that Pick disease is one of the causes of FTD syndromes including behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), and corticobasal syndrome (CBS). However, until recently, the disease pattern and clinical FTD symptoms associated with Pick disease were not well defined: identification of Pick disease can only occur post mortem, and prior post mortem studies lacked detailed clinical information about patient symptoms.

Dr. Irwin addressed this gap in knowledge by analyzing brain tissue samples of patients with Pick disease in conjunction with detailed clinical information. His findings indicated that Pick disease may originate in the limbic region (important to emotion, behavior, and memory) of the frontotemporal lobes, suggesting this brain region as an early target of Pick disease. He found that from this region, Pick disease appears to progress to the frontal and temporal lobes, regions at the base of the brain, and to the occipital lobes located at the back of the brain. By analyzing the clinical information acquired during a patient’s life, Dr. Irwin also found that most patients with Pick disease had bvFTD and that all patients with Pick disease featured some symptoms of impaired social behavior. 

In addition to describing the pattern and symptoms of Pick disease in FTD, Dr. Irwin also developed a novel method to quantify the severity of Pick disease in brain tissue samples using digital image analysis. Traditional analysis of brain tissue requires that each tissue sample be examined under the microscope and rated on a scale ranging from 0 (‘no disease’) to 3 (‘severe disease’). To more efficiently and precisely analyze brain tissue samples, Dr. Irwin took digital images of these microscope slides of samples and developed a mathematical algorithm for a computer to count the number of Pick bodies in each digital image. Then, digital counts were compared to counts of Pick bodies done by hand in each microscope slide in order to validate the method.

Results showed that the two methods of counting were very similar, indicating that the digital image analysis was a success. This new method is an important tool for researchers studying Pick disease and other FTD-associated diseases, and will enable more rapid analysis of brain tissue samples.

Together, the findings of Dr. Irwin’s research studies will help researchers in the FTD community to better characterize Pick disease, with the goal of improving the ability to diagnose biologic causes of FTD, which is critical for testing emerging disease-modifying therapies.

We thank the patients and their families, without whose meaningful contributions this work would not be possible.

For more information on participation in the Brain Bank program, please contact:
Anna Yung, RN, BSN, at the Penn FTD Center by telephone at 215-662-3361 or by email at anna.yung@uphs.upenn.edu
Kevin Davies at the Center for Neurodegenerative Disease Research by telephone at 215-662-4474 or by email at daviesk@upenn.edu

If you’d like to read more about the pattern of Pick disease in the brain, please visit:
http://www.ncbi.nlm.nih.gov/pubmed/26583316

If you’d like to read more about digital image analysis of Pick disease, please visit:
http://www.ncbi.nlm.nih.gov/pubmed/26538548

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