Marek-Marsel Mesulam of Northwestern University in Chicago wins this year’s Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Diseases. Supported by philanthropic donations from the Potamkin family of Colorado, Philadelphia, and Miami, the $100,000 prize goes to researchers who make critical advances in neurodegenerative disease research. Mesulam received the award for his contributions to the discovery and understanding of primary progressive aphasia (PPA). His work showed that this language disorder can manifest differently in people with Alzheimer’s disease and frontotemporal dementia. Mesulam received the award April 30 at the 2014 American Academy of Neurology meeting held April 26 through May 3 in Philadelphia.

Mesulam first described PPA in 1982, in a paper describing six patients who had language difficulties that progressed slowly in the absence of dementia (see Mesulam, 1982). Even that small study hinted that the disorder was quite heterogeneous, as some of the patients only had trouble recalling words, whereas one could not understand language at all. Mesulam and others built upon these initial findings over the next three decades, and now PPA is classified into three clinical subcategories: agrammatic aphasia (difficulty constructing sentences that are grammatically correct), semantic aphasia (difficulty recalling words), and logopenic aphasia (delayed or uneven speech due to slow word retrieval).

While PPA symptoms may appear in the absence of dementia, Mesulam’s work ultimately helped show that the different forms of PPA are caused by underlying neurodegenerative disease. Mesulam and others have observed profound degeneration in the left hemisphere of the brain in people with PPA, and found that around 30 percent of PPA cases had frontotemporal lobular degeneration (FTLD) with tauopathy, another 30 percent had FLTD with TDP-43 aggregate pathology, and the remaining 40 percent displayed the characteristic Aβ deposits and neurofibrillary tangles of AD. Interestingly, his studies also revealed an odd pattern of neurofibrillary tangles in AD patients with PPA as compared with others with the disease. Those with PPA had tangles that skewed toward the language centers of the neocortex, rather than the entorhinal cortex (see Gefen et al., 2012, and Mesulam et al., 2014). While the reasons behind the variety of PPA manifestations aren’t known, Mesulam reported that people with learning disabilities have a heightened risk of developing PPA (see Feb 2008 news story). He hypothesized that damage to neuronal networks, rather than brain atrophy alone, may account for PPA symptoms (see Nov 2010 conference coverage).—Jessica Shugart

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References

News Citations

  1. Primary Progressive Aphasia—Learning Disabilities Point to Early Susceptibility
  2. Indianapolis: Neuroimaging Opens Window to Disease, Better Diagnosis

Paper Citations

  1. . Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982 Jun;11(6):592-8. PubMed.
  2. . Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain. 2012 May;135(Pt 5):1554-65. PubMed.
  3. . Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in primary progressive aphasia. Brain. 2014 Apr;137(Pt 4):1176-92. Epub 2014 Feb 25 PubMed.

Further Reading