Presenilin 1 Mutation G209E Implicated in Familial Early Onset Alzheimer Disease

In families with Early onset Alzheimer Disease (EOAD), mutations in the PSEN1 gene are commonly implicated in the development of neurodegeneration. In this study, we present the clinical and neuropathological findings observed in a family with a PSEN1 G209E mutation. Four different mutations at the codon can result in the substitution of Arginine (R), Valine (V), Alanine (A), or Glutamic acid (E), for Glycine (G). The mutations have been linked with EOAD and we will discuss the clinicopathological pattern associated with each mutation with an emphasis on G209E pathology which is not well researched. Review of the clinical records revealed an age of onset of 38 with presentation of memory decline, apathy, mild parkinsonism, and aggressiveness over the course of the disease. Neuropathologically, proband showed severe AD with neurofibrillary tangles at a Braak stage of 6 and β-amyloid (Aβ) plaques with an amyloid score of A3. Additionally, amyloid angiopathy and atypical perivascular Aβ pathology were observed. Severe plaque and tau pathology were also discovered in areas controlling motor coordination and eye movement, suggesting clinical correlations beyond the typical AD presentation. The case findings suggest G209E is pathogenic for AD with a clinical presentation unique from G209R, G209V, and G209A.

Supervisors: Dr. Ghetti, Dr. Newell, and Mr. Jacobsen
Department: Pathology and Laboratory Medicine