Blinded comparison of different alpha-synuclein seeding assays as cutaneous biomarkers of lewy body dementias

Ended Project Grant Awarded Last action

Award ID
R01NS118669
Recipient
Awarding agency
Obligated
$4,771,373

Award facts

Assistance listing
93.866 Aging Research
Completion date
Originally
Funding
  • $4,150,109.00 Federal
  • $621,264.00 Non-federal
Funding agency
National Institute on Aging National Institutes of Health, Department of Health and Human Services
Place of performance
Arizona, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
With increasing longevity in our population, dementia is widely recognized as an impending public health crisis. Lewy body dementia (LBD), encompassing dementia with lewy bodies (DLB) and parkinson disease dementia (PDD), is the second most common cause. LBD is characterized by abnormal aggregation and accumulation of a protein, a-synuclein (asyn). PDD and DLB are clinically separated only by the relative timing of the onset of parkinsonism and dementia. At present, advances in the treatment of these conditions are critically hampered by the lack of non-invasive, inexpensive biomarkers that can provide accurate diagnostic and prognostic information. This situation may soon be resolved, as in recent years IT has become apparent, through our own studies and those of others, that biopsies of peripheral tissue sites can detect diagnostically significant asyn. Our project will assess asyn in punch biopsies of the skin. Our preliminary data from new "seeding assay" methods including real-time quaking-induced conversion (RT-quic) and protein misfolding cyclic amplification (pmca), from autopsy-confirmed LBD subjects, indicate high sensitivity and specificity for predicting the presence of asyn in the skin of affected subjects. Further work is necessary to confirm these results in living subjects with these conditions, which is the objective of this proposed project. We will biopsy, twice during a four year period, 90 subjects with asyn disease, 30 each with PD, PDD and DLB, as well as 30 normal control subjects. Two independent laboratories will blindly perform separately-developed seeding assays, rigorously testing the interlaboratory reliability and providing estimates of asyn density change over time. The seeding assay results will be compared with those obtained by the current gold-standard biopsy method, immunohistochemistry (IHC). All subjects will receive cognitive and movement disorder assessments at two timepoints in this four year project, enabling comparisons of assay measures with cognitive and motor decline rates. Many of the subjects will be enrolled in the arizona study of aging and neurodegenerative disorders (azsand), a longitudinal clinicopathological study with an autopsy rate exceeding 90%. This will allow, in a substantial subset, eventual neuropathological confirmation of the molecular cause of parkinsonism and dementia in each subject.

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $571,411 $0
Amendment $569,916 $0
Amendment $572,495 $0
Amendment $572,495 $0
Amendment $0 $0
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Amendment $621,264 $0
Amendment $621,264 $0
Original award $621,264 $621,264
Show all 11

Subawards

Subrecipient Amount Awarded
University Of Georgia Research Foundation, Inc. Dr. Anumantha Kanthasamy and his researchers at the University of Georgia (UGA) will carry out the following work. Two skin biopsies from back of the neck of 60… $191,250
Mayo Clinic Arizona Amendment 3&4 authorized $94,284 for budget period 4's period of performance through 08/31/2025. $94,284
Dignity Health Dr. Shill and Barrow Neurological Institute will recruit study subjects to participate in the study. Dr. Shill and staff will perform the required examination… $59,000
Mayo Clinic Drs. Brad Boeve and Kejal Kantarci from Mayo Clinic Rochester will be recruiting and collecting clinical data and skin biopsies from at least 20 subjects with… $44,913
Mayo Clinic Jacksonville (A Nonprofit Corporation) Neill Graff-Radford and Zbigniew Wszolek from Mayo Clinic Jacksonville will be recruiting and collecting clinical data and skin biopsies from at least 10… $37,591

Quick answers

Who received award R01NS118669?

R01NS118669 was awarded to Banner Health by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on September 15, 2021.

How much is award R01NS118669 worth?

$4,771,373 has been obligated on R01NS118669: $4,150,109 in federal funding and $621,264 in non-federal funding.

Which agency awarded R01NS118669?

National Institute of Neurological Disorders and Stroke (National Institutes of Health) awarded R01NS118669, with funding from National Institute on Aging (National Institutes of Health).

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