Abstract: The present disclosure provides methods and materials for screening a compound or monitoring a subjects response to a compound or dosing regimen for treating frontotemporal dementia (FTD). Methods and materials for identifying and treating a subject having FTD are also provided.

Abstract: Provided herein are fusion proteins that comprise progranulin and an Fc polypeptide. Methods of using such proteins to treat progranulin-associated disorders (e.g., a neurodegenerative disease, such as frontotemporal dementia (FTD)) are also provided herein.

Abstract: Certain embodiments described herein provide a method for treating dysregulated lipid metabolism and/or inflammation in a mammal in need thereof, comprising administering to the mammal an effective amount of an agonist anti-triggering receptor expressed on myeloid cells 2 (TREM2) antibody.

Abstract: Certain embodiments provide a method of detecting one or more biomarkers in a subject having a lysosomal storage disorder, the method comprising: 1) measuring the concentration of a combination of two or more lipids in a sample from the subject, wherein the combination of lipids is selected from the group consisting of: a) a bis(monoacylglycero)phosphate (BMP); b) a GM2 ganglioside and/or a GM3 ganglioside; c) a GD3 ganglioside; d) a GD1a/b ganglioside; and e) a glucosylceramide (GlcCer); 2) measuring the concentration of GlcCer in a sample from the subject; 3) measuring the concentration of neurofilament light chain (Nf-L) in a sample from the subject; and/or 4) measuring the concentration of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in a sample from the subject.

Abstract: Certain embodiments described herein provide a method for treating dysregulated lipid metabolism and/or inflammation in a mammal in need thereof, comprising administering to the mammal an effective amount of an agonist anti-triggering receptor expressed on myeloid cells 2 (TREM2) antibody.

Abstract: The present disclosure provides methods and materials for screening a compound or monitoring a subjects response to a compound or dosing regimen for treating a PGRN-associated disorder. Methods and materials for identifying and treating a subject having a PGRN-associated disorder are also provided.

Abstract: Provided herein are fusion proteins that comprise progranulin and an Fc polypeptide. Methods of using such proteins to treat progranulin-associated disorders (e.g., a neurodegenerative disease, such as frontotemporal dementia (FTD)) are also provided herein.

Abstract: In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody increases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody decreases levels of sTREM2. In some embodiments, the antibody enhances TREM2 activity. In some embodiments, the antibody inhibits TREM2 activity.

Abstract: The present invention relates to the use of agents that inhibit the toxic effects of amyloid oligomers by increasing intracellular levels of phosphoinositol 4-phosphate (PI(4)P, or “PIP”) and/or phosphotidylinositol 4,5-biphosphate (PI(4,5)P2 or “PIP2”), the use of such agents for the treatment of neurodegenerative diseases, methods of treating neurodegenerative diseases by administration of agents which alter lipid metabolism, and methods of identifying agents which alter the association of presenilins with ?-secretase and lipid rafts.