Biomarkers

A method of mapping a motoneuron disease, with or without dementia, or a dementia (Alzheimer's disease) to a specific location in the brain, the method comprising

• a) administering an isotope-labeled substrate to a subject afflicted with a known motoneuron disease, with or without dementia, or a known dementia (Alzheimer's disease), for a period of time sufficient for said isotope-labeled substrate to enter into one or more cargo molecules in axons of motor neurons;
• b) administering an isotope-labeled substrate to a subject not afflicted with the motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease), for a period of time sufficient for said isotope-labeled substrate to enter into one or more cargo molecules in axons of motor neurons or other subpopulations of neurons;
• c) obtaining a plurality of samples from the subject afflicted with the known motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease);
• d) obtaining a plurality of samples from the subject not afflicted with the motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease);
• e) comparing the time course, pattern or amount of isotopic enrichment in said isolated vesicle cargo molecules in the subject afflicted with the known motoneuron disease, with or without dementia, or a dementia (Alzheimer's disease), with the time course, pattern or amount of isotopic enrichment in said isolated vesicle cargo molecules in the subject not afflicted with the motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease),
• f) determining the one or more cargo molecules that are present in the samples from the subject afflicted with the known motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease), that are not present in the samples from the subject not afflicted with the motoneuron disease, with or without dementia, or the dementia (Alzheimer's disease).

A method of diagnosing a motoneuron disease, with or without dementia, or a dementia (Alzheimer's disease), of a specific location in the brain, the method comprising

• a) administering an isotope-labeled substrate to said living system for a period of time sufficient for said isotope-labeled substrate to enter into one or more cargo molecules in axons of motor neurons;
• b) obtaining a plurality of samples from said living system;
• c) quantifying the time course, pattern or amount of isotopic enrichment in one or more secreted vesicle cargo molecules from said plurality of samples;
• d) measuring the time course, pattern or amount of isotopic enrichment in secreted vesicle cargo molecules in a sample from a control system;
• e) comparing the time course, pattern or amount of isotopic enrichment in said isolated vesicle cargo molecules in said living system to the same parameters in a control living system;
• and
• f) determining the effect of said agent on the rate of microtubule (MT)-mediated slow and fast axonal transport in motor neurons or other subpopulations of neurons.

A method of diagnosing a motoneuron disease, with or without dementia, or a dementia (Alzheimer's disease), the method comprising

• a) administering an isotope-labeled substrate to said living system for a period of time sufficient for said isotope-labeled substrate to enter into one or more cargo molecules in axons of motor neurons or other subpopulations of neurons;
• b) obtaining a plurality of samples from said living system;
• and
• c) quantifying the time course, pattern or amount of isotopic enrichment in one or more secreted vesicle cargo molecules from said plurality of samples,
• wherein one or more secreted vesicle cargo molecules are selected from the group consisting of chromogranin B, proenkephalin A, neurosecretory VGF, and clusterin;
• wherein the motoneuron disease with or without dementia, or a dementia (Alzheimer's disease), is a selected from a group comprising PD, PDD, and ADD.