Partner Research Centers:


Center for Neurodegenerative Disease Research

Disease Approach

Neurodegenerative diseases share many common pathways and mechanisms, making the coordinated study of these diseases both necessary and highly productive. The components of CNDR research programs are linked into a unified conceptual framework by the hypothesis that "diverse neurodegenerative diseases arise from 'fatal attractions' of brain proteins."

Here are brief explanations of the major diseases being explored at CNDR.

Alzheimer's Disease

Alzheimer's disease or AD, the most common cause of dementia in the elderly, is a heterogeneous group of neurodegenerative disorders. Scientists at CNDR are attempting to identify how the two hallmark brain lesions of AD – plaques accumulating around brain cells and composed of aggregates of a protein called Β-amyloid; and neurofibrillary tangles, composed of a protein called tau and are found inside of the neurons – form and whether interrupting this process would prevent neurodegeneration and dementia. The team is also working on ways to detect the presence of disease pathology at the earliest stages, and identifying targets to try to stop the disease from progressing.

Patients and families can reach out to the Penn Alzheimer's Disease Center for information on clinical trials and care. For more information on Alzheimer's disease, visit the National Institute on Aging and the Alzheimer's Disease Education and Referral Center (ADEAR), or the Alzheimer's Association.

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Frontotemporal Degeneration (FTD)

FTD is a complex group of disorders characterized by shrinkage of the frontal and anterior temporal lobes of the brain. It is the second most common cause of dementia in people under the age of 65, after AD. CNDR researchers discovered in 2006 a link between FTD and Amyotrophic Lateral Sclerosis (ALS). In both diseases, study of brain tissue revealed accumulations of a misfolded protein called TDP-43. Now these scientists are trying to understand the basic biology of TDP-43 and the mechanisms that lead to the formation of aggregates.

Patients and families with FTD disorders can consult experts at the Penn FTD Center, led by Murray Grossman, MD.

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Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive neurodegenerative disease that affects upper and lower motor neurons in the brain and spine, resulting in lost control of the muscles. In 2006, CNDR researchers discovered, in the brain tissue of people who had died from sporadic forms of ALS, accumulations of a misfolded protein called TDP-43, linking the motor neuron disease with frontotemporal degeneration. CNDR scientists have also found two families with familial ALS in which mutations in the gene for TDP-43 tracked with the disease, further supporting the idea that TDP-43 plays an important role in ALS and FTD.

The ALS Association-supported ALS Center at Pennsylvania Hospital provides multidisciplinary evaluation and treatment of patients with amyotrophic lateral sclerosis (ALS) and related motor neuron disorders.

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Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Scientists at CNDR are studying several possible mechanisms that may explain how a mutation or toxin could cause the death of neurons supplying dopamine to the nervous system. In the brains of people who died from PD, scientists have found abnormal accumulations of a protein called alpha-synuclein. Most recently, CNDR researchers have shown that alpha-synuclein can spread from cell-to-cell within the brain, and scientists are now working on targeted treatment options that prevent the transmission of toxic proteins.

With the designation of the Morris K. Udall Parkinson's Disease Research Center of Excellence from the National Institute of Neurological Disorders and Stroke (NINDS), Penn joins other Udall Centers at universities across the U.S., each actively investigating Parkinson's or a specific aspect of Parkinson's disease. The NINDS funding allows Penn to unite the many talented clinicians and researchers engaged in Parkinson's research under one coordinated roof – pulling from the Parkinson's Disease & Movement Disorders Center, the Parkinson's Disease Research, Education & Clinical Center at the Philadelphia VA Medical Center (PADRECC); the Institute on Aging (IOA), and the Center for Neurodegenerative Disease Research (CNDR).

The Parkinson's Disease and Movement Disorders Center at Pennsylvania Hospital provides clinical trials and full-service care to patients with PD. The team collaborates on translational research efforts with CNDR researchers.

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Lewy Body Disorders

Lewy bodies, abnormal clumps of protein found in the brains of people with PD, are also found in other dementing illnesses that go by the names Dementia with Lewy Bodies (DLB), and the Lewy body variant of Alzheimer's disease (LBVAD). DLB can be difficult to distinguish from AD or PD with dementia (PDD). One difference is that people with DLB often have hallucinations. In addition, people with DLB react very poorly to anti-psychotic medications such as Haldol and Thorazine. Also, while people with DLB may have Parkinsonian symptoms, the dementia usually appears first, while most people with PDD develop dementia later in the disease course. Individuals with DLB also can have fluctuating cognition, a characteristic vacillation of attention, and unlike individuals with AD, persons with DLB can have REM Sleep Behavior Disorder.

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