Abstract: Methods of detecting the signature of Alzheimer's disease before the clinical onset of the disease are disclosed, such as methods of diagnosing Mild Cognitive Impairment (MCI), monitoring the progress of MCI, and predicting the time to clinical onset of AD dementia. The methods use a Biomarker Severity Score, which corresponds to output signals of one or more biomarkers chosen from AD Index, Morphometric Imaging, and PKC Epsilon Biomarkers. Also disclosed are methods of screening for a compound useful for treating MCI or for preventing the clinical onset of AD dementia, as well as methods of evaluating or monitoring the therapeutic benefit of an agent for treating MCI or preventing the clinical onset of AD dementia.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods employ the steps of (a) culturing a subject's lymphocytes with a suitable basement membrane matrix to permit the lymphocytes to aggregate; (b) measuring the resulting lymphocyte aggregation; and (c) based on such measurement, either diagnosing Alzheimer's disease or determining a predisposition to it, as appropriate.

Abstract: A method for treating or preventing amyotrophic lateral sclerosis (ALS) or other motor neuron disease in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the motor neuron disease by activating PKC in the subject. The ALS may be, for example, classical ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.

Abstract: A method for treating nerve damage in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of a PKC activating therapeutic agent (e.g., bryostatin compound or analogue thereof or PUFA compound or derivative thereof) on a weekly dosage regimen to result in at least partial repair or regeneration of damaged nerves in the subject, wherein the weekly dosage regimen comprises a dosage of about 10 to about 60 ?g/m2 once a week for at least two weeks, wherein the at least two weeks of dosing are done consecutively or intermittently. The subject may have, for example, spinal cord injury, cochlear nerve damage, or nerve damage to direct peripheral nerves, such as in the extremities.

Abstract: Methods of detecting the signature of Alzheimer's disease before the clinical onset of the disease are disclosed, such as methods of diagnosing Mild Cognitive Impairment (MCI), monitoring the progress of MCI, and predicting the time to clinical onset of AD dementia. The methods use a Biomarker Severity Score, which corresponds to output signals of one or more biomarkers chosen from AD Index, Morphometric Imaging, and PKC Epsilon Biomarkers. Also disclosed are methods of screening for a compound useful for treating MCI or for preventing the clinical onset of AD dementia, as well as methods of evaluating or monitoring the therapeutic benefit of an agent for treating MCI or preventing the clinical onset of AD dementia.

Abstract: The present disclosure describes novel PKC-? activators chosen from halogenated esters of unsaturated fatty acids and derivatives thereof, including halogenated esters of both polyunsaturated and monounsaturated fatty acids and derivatives thereof. The disclosure further relates to compositions, kits, and methods for treatment using the halogenated esters.

Abstract: A method for treating or preventing mild, moderate, or advanced multiple sclerosis (MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to result in mitigation or prevention of demyelination, initiation of remyelination, or reduction or prevention of neuroinflammation in early MS. The MS may be, for example, relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.

Abstract: A method for treating or preventing optic nerve inflammation or other neurological inflammation or associated disorder (e.g., early MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the neurological inflammation by activating PKC in the subject. The optic nerve inflammation may be, for example, optic neuritis, neuromyelitis optica, or diabetic papillopathy, any of which may be acute, subacute, or nascent. The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.

Abstract: The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Abstract: Dosing regimens and methods are disclosed for upregulating protein kinase C (PKC) while reducing subsequent downregulation, comprising administering a PKC activator once a week for three consecutive weeks followed by cessation of administration or dosing for three consecutive weeks. Also described are methods for improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.

Abstract: The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Abstract: This invention provides a method for determining whether a human subject is afflicted with AD or non-ADD when the subject is suspected of being afflicted with AD or non-ADD, comprising the steps of (a) synchronizing a population of suitable cells derived from the subject; and (b) in the resulting synchronized cell population, measuring the expression level of a gene known to be differentially expressed between corresponding synchronized cells derived from AD patients and those derived from non-ADD patients, whereby (i) the subject is afflicted with AD if the expression level measured in step (b) is consistent with that gene's expression level in corresponding synchronized cells derived from AD patients, and (ii) the subject is afflicted with non-ADD if the expression level measured in step (b) is consistent with that gene's expression level in corresponding synchronized cells derived from non-ADD patients. This invention also provides diagnostic methods based on NDS patient gene expression levels.

Abstract: The present invention relates to methods of diagnosing Alzheimer's Disease in a human patient by detecting alterations in the ratio of PKC epsilon protein levels in a human patient compared with PKC epsilon levels in a control subject. The Alzheimer's disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's disease and for screening methods for the identification of compounds for treating or preventing Alzheimer's disease. The present invention also provides methods for elevating PKC epsilon protein levels comprising the steps of contacting one or more human cells with an amount of a PKC activator effective to elevate PKC epsilon levels compared to an uncontacted human cell.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods involve the steps of (a) culturing lymphocytes from the subject under suitable conditions; (b) measuring the amount of PKC? in the cultured lymphocytes; and (c) comparing the measurement of step (b) with a suitable control.

Abstract: A method for inducing synaptogenesis in a subject having a neurodegenerative disease, the method comprising administering an angiotensin or analogue thereof in a therapeutically effective amount to induce synaptogenesis in said subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.

Abstract: The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods employ the steps of (a) culturing a subject's lymphocytes with a suitable basement membrane matrix to permit the lymphocytes to aggregate; (b) measuring the resulting lymphocyte aggregation; and (c) based on such measurement, either diagnosing Alzheimer's disease or determining a predisposition to it, as appropriate.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods employ the steps of (a) culturing a subject's lymphocytes with a suitable basement membrane matrix to permit the lymphocytes to aggregate; (b) measuring the resulting lymphocyte aggregation; and (c) based on such measurement, either diagnosing Alzheimer's disease or determining a predisposition to it, as appropriate.

Abstract: The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Abstract: A method for treating or preventing amyotrophic lateral sclerosis (ALS) or other motor neuron disease in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the motor neuron disease by activating PKC in the subject. The ALS may be, for example, classical ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.