Marek-Marsel Mesulam, MD, on Aphasia in Alzheimer Disease

Primary progressive aphasia (PPA) is associated with a form of Alzheimer disease (AD) but is not linked with ApoE4 like amnestic forms of AD, according to a new study. The study will be part of a presentation at the 144th Annual Meeting of the American Neurological Association in October 2019.1

Speaker and lead researcher Marek-Marsel Mesulam, MD, answered our questions about his work.

Dr Mesulam is the director of the Mesulam Center for Cognitive Neurology and Alzheimer's Disease, chief of Behavioral Neurology in the Department of Neurology, the Ruth Dunbar Davee Professor of Neuroscience, and a professor of neurology (behavioral neurology) at the Feinberg School of Medicine at Northwestern University.

NEUROLOGY CONSULTANT: Your study found 3 pathologies for AD. Of the 107 PPA patients you autopsied, 36% had the pathology of FTLD-tau, 35% had AD, and 25% had FTLD-TDP. How might PPA affect AD or vice versa? Can treating one prevent or delay the other?

Marek-Marsel Mesulam: PPA refers to a clinical syndrome where a language disturbance emerges in relative isolation and becomes the principal reason that brings the patient to medical attention. AD in this context refers to the amyloid and tau neuropathology that destroys neurons in the language-dominant (usually left) hemisphere of the brain. Symptomatic treatment of the PPA does not alter the AD pathology. However, treatment of AD by cholinesterase inhibitors or through clinical trials may delay the neurodegeneration and may lead to symptomatic improvement or slowing of progression.

NEURO CON: Your findings showed that AD is not uniform and that is has subtypes—one of which can lead to PPA. Which subtype of AD leads to PPA, and what do practicing neurologists need to know about this connection?

MMM: Typical AD preferentially destroys memory areas in the medial temporal lobe. This is why typical AD causes an amnestic dementia. In typical AD, ApoE4 is the most important molecular risk factor. The form of AD that causes PPA has a different pattern. The neurofibrillary pathology may be more intense in language-related neocortical areas than in memory-related limbic areas, and ApoE4 is not a major risk factor. 

NEURO CON: How might your study results affect clinical practice or change the way PPA is managed?

MMM: PPA is a distinct syndrome that needs to be diagnosed accurately. Symptomatic interventions should focus on speech therapy rather than memory training. PPA patients with positive biomarkers for AD should be considered for cholinesterase inhibitor therapy and for inclusion in AD-related clinical trials.

For more information about the ANA’s Annual Meeting or to read more about Dr Mesulam’s session, visit the ANA’s website: https://2019.myana.org.



  1. Mesulam MM. Recent advances in PPA. Talk will be presented at: ANA 2019; October 13-15, 2019: St. Louis, MO. https://2019.myana.org/sites/default/files/docs/2019/ana19_advanceprogram.pdf.