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• W1564335978 abstract "OBJECTIVE: To evaluate if APOE4 status may contribute to misdiagnosis of Alzheimer’s Disease (AD) and Frontotemporal Degeneration (FTD).BACKGROUND: FTD and AD are pathologically distinct neurodegenerative diseases but have considerable clinical overlap that make accurate diagnosis challenging. APOE4 is a genetic risk factor associated with late-onset AD that can influence clinical presentation, but has received little attention in FTD. We assessed whether APOE4 status contributes to misdiagnosis of AD and FTD.DESIGN/METHODS: Clinically diagnosed AD (n=545) and FTD (n=263) patients received a neuropathological diagnosis using either a cerebrospinal fluid (CSF) lumbar puncture or a detailed neuropathological exam at autopsy. A previously autopsy-validated CSF total-tau to beta-amyloid ratio was used to classify patients as AD (>0.34) or FTLD (<0.34) pathology. DNA samples were collected via blood draw using standard methods to determine APOE4 genotype. We categorized patients as carriers of an E4 allele (APOE4+) or non-carriers (APOE4-).RESULTS: An evaluation of clinical diagnosis accuracy revealed that 84% of patients with clinical AD or FTD were correctly classified as having AD or FTLD pathology. An examination of APOE4 status in clinical AD revealed that 66% (n =330/498) of patients correctly classified as having AD pathology were APOE4+ while only 43% (n=20/47) of misclassified cases were APOE4+. In contrast, 25% (n=47/184) of clinical FTD patients correctly classified as having FTLD pathology were APOE4+ while 35% (n=28/79)of misclassified cases were APOE4+. Together, these findings suggest misclassified AD cases are more likely to be APOE4- (X2=13.28; p=.001) while misclassified FTD cases are more likely to be APOE4+ (X2=5.66; p=.05).CONCLUSION: Our findings suggest that APOE4 status may influence the clinical presentation of AD or FTD and thus may contribute to pathological misdiagnosis. Future investigations should identify clinical features associated with APOE4 in AD and FTD that may facilitate differential diagnosis.This work was supported by the Wyncote Foundation and NIH: AG043503, AG017586, AG032953, AG038490, NS044266, NS053488. Disclosure: Dr. Haley has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Wood has nothing to disclose. Dr. Wolk has received personal compensation for activities with Exponent, Inc. as a consultant; and Haymarket Medical Education as CME faculty. Dr. Trojanowksi has received personal compensation for activities with Pfizer Inc., Johnson & Johnson, MetLife, and Bristol-Myers Squibb Co. as a consultant. Dr. Trojanowski has received royalty payments through Penn licenses. Dr. Trojanowksi has received research support from AstraZeneca and Bristol-Myers Squibb Co. Dr. Shaw has received personal compensation for activities with Innogenetics/Fujirebio, Janssen, and Saladax. Dr. Van Deerlin has nothing to disclose. Dr. Grossman has received personal compensation for activities with Allon Therapeutics." @default.
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• W1564335978 date "2014-04-08" @default.
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• W1564335978 title "Learning from Our Mistakes: APOE4 Influences Misdiagnosis of Alzheimer’s Disease and Frontotemporal Degeneration (P5.208)" @default.
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