Abstract Details

Title Novel CSF Tau Assays Demonstrate Different Abnormalities in Severity-Matched Alzheimer's Disease and Progressive Supranuclear Palsy

Topic Aging and Dementia

Presentation(s) S34 - (-)

Poster/Presentation
Number 006

Objective

Background CSF tau and phosphorylated tau (ptau) levels are elevated in AD and are thought to reflect neuronal loss. However, tau and ptau levels have previously been reported to be normal in PSP using the standard CSF tau assays.

Design/Methods We used the standard INNO-BIA AlzBio3 multiplex immunoassay to measure CSF A?, tau, and ptau181, and two novel sandwich ELISAs targeting a different central tau epitope (HT7-BT2) and a different ptau epitope (HT7-p231), in 30 normal control (NC), 32 AD, and 11 PSP patients. AD and PSP were matched for severity using CDR-SB scores.

Results Using the standard AlzBio3 assay, total tau levels were elevated in AD as compared to controls (p=0.002), and PSP patients (p=0.014), with PSP patients similar to controls (p=0.95). AD also displayed higher ptau levels than NC (p<0.001), and PSP (p=0.006). Using the HT7-BT2 ELISA, AD subjects exhibited higher central tau fragment levels as compared to PSP (p=0.001) with a trend towards higher levels than NC (p=0.105). In contrast, in PSP there was a trend towards lower central fragment levels as compared to NC (p=0.074). pTau231 levels were highest in PSP (p=0.005 vs NC), but were also elevated in AD (p=0.01 vs NC).

Conclusions Changes in CSF tau fragments are different in PSP than in AD despite the presence of severe tau pathology in both disorders. This suggests that the relationship between CSF tau and neurodegenerative disease is a complex process potentially reflecting multiple factors related to the underlying cause of the tauopathy and neuronal dysfunction that may not adequately captured by current models.

Authors/Disclosures
Dana Wagshal, PhD (U of California, San Francisco) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Anna Karydas (UCSF)	No disclosure on file
	No disclosure on file
	No disclosure on file
Joel Kramer, PhD (UCSF Medical Center)	The institution of Dr. Kramer has received research support from tau consortium. Dr. Kramer has received publishing royalties from a publication relating to health care.
Jens Schmidt, MD, FAAN (University Hospital Brandenburg Medical School / Immanuel Klinik Rüdersdorf)	Dr. Schmidt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring and UCB. Dr. Schmidt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring and LFB. Dr. Schmidt has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Dr. Schmidt has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Schmidt has received research support from Kezar, Novartis and AFM.
Gil D. Rabinovici, MD, FAAN (UCSF Memory & Aging Center)	Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Norodisk. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for C2N. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Peerview. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer's Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with ANA.
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.
	No disclosure on file
Adam L. Boxer, MD, PhD (University of California, San Francisco)	An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project. Dr. Boxer has received research support from Rainwater Charitable Foundation.

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