Methods and compositions to detect the level of lysosomal exocytosis activity and methods of use

A method of diagnosing cancer in a subject, the method comprising:

• a) providing a subject profile comprising a lysosomal sialidase activity profile comprising two or more values from different lysosomal sialidase activity markers, a NEU1 substrate sialylation activity profile or a NEU1 level activity profile from a tumor sample from said subject;
• b) providing a corresponding reference profile comprising a NEU1 activity profile comprising two or more values from different lysosomal sialidase activity markers, a NEU1 substrate sialylation activity profile or a NEU1 level activity profile from a control sample, wherein the subject profile and the reference profile comprise one or more values representing lysosomal sialidase activity, NEU1 substrate sialylation activity or NEU1 level activity;
• and
• c) comparing said subject and said reference lysosomal sialidase activity profiles to thereby determine the diagnosis for said subject, wherein said subject is diagnosed with cancer if said lysosomal sialidase activity of said subject is lower, the NEU1 substrate sialylation activity is higher or the NEU1 level activity is higher than the lysosomal sialidase activity, NEU1 substrate sialylation activity or NEU1 level activity of said reference.

A method of determining the prognosis for a lysosomotropic chemotherapeutic agent regime in a subject with cancer, comprising the steps of

• a) providing a subject lysosomal sialidase activity profile from a tumor sample from said subject;
• b) providing a reference lysosomal sialidase activity profile from a control sample, wherein the subject lysosomal sialidase activity profile and the reference lysosomal sialidase activity profile comprise one or more values representing lysosomal sialidase activity;
• and
• c) comparing said subject and said reference lysosomal sialidase activity profiles to thereby determine the prognosis for a lysosomotropic chemotherapy agent regime in the subject, wherein a lower lysosomal sialidase activity of said subject as compared to the lysosomal sialidase activity of said reference results in a prediction that said cancer will be resistant to said lysosomotropic chemotherapeutic agent.

A method of diagnosing dementia associated with Alzheimer's disease in a subject, the method comprising:

• a) providing a subject lysosomal exocytosis activity profile of a sample of cerebrospinal fluid from said subject;
• b) providing a reference lysosomal exocytosis activity profile of a control sample of cerebrospinal fluid, wherein the subject lysosomal exocytosis activity profile and the corresponding reference lysosomal exocytosis activity profile comprise one or more values representing lysosomal exocytosis activity;
• and,
• c) comparing said subject and said reference lysosomal exocytosis activity profiles, wherein said subject is diagnosed with dementia associated with Alzheimer's disease if the subject has a higher lysosomal exocytosis activity as compared to the reference lysosomal exocytosis activity.