Targeting lysosomal lipid in alzheimer's disease
AssigneeThe University of North Carolina at Chapel Hill
InventorsLeon G. Coleman, JR., Alexandra Barnett, Zibo Li, Saradhi Kalari, Xinrui Ma
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Abstract
Novel lysosomal acid lipase (LAL) positron emission tomography ligands are provided. Also disclosed herein are methods of assessing the risk of developing Alzheimer's disease (AD) or Alzheimer's Disease Related Dementias (ADRD) and methods of diagnosing AD/ADRD in a subject comprising measuring levels of LAL and optionally LAL accumulation in the subject. Methods of treatment comprising administering LAL are also provided.
Claims30
A lysosomal acid lipase (LAL) positron emission tomography (PET) ligand according to:
- wherein X is C, CH, CH2, CR2, S, N, or O,
- wherein R1 can be substituted at one or more positions on the piperidyl ring and each R1 is independently a C1-C5 alkyl, C1-C5 cyano, C1-C5 amide group, a linker (e.g., a PEG linker or an arene-containing linker), or a halogen, and comprises a radioisotope, and
- wherein R2 comprises a radiolabel.
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A method of diagnosing or assessing the risk of developing Alzheimer's disease (AD) or Alzheimer's Disease Related Dementias (ADRD) in a subject, the method comprising:
- a) measuring the amount and/or activity of lysosomal acid lipase (LAL) in the subject;
- b) comparing the amount and/or activity of LAL measured in (a) with a threshold amount and/or activity of LAL;
- and
- c) diagnosing AD or ADRD or identifying an increased risk of developing AD or ADRD based on the amount and/or activity of LAL measured in (a) being lower than the threshold amount and/or activity of LAL.
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Dependencies are inferred from the claim text.