Aggregation Deposition Tau protein (NFT) Amyloid Precursor Protein Neuronal & Synaptic dysfunction Cholinergic Neurons (hippocampus, etc) Inflammation Incipient Stage of AD Irreversible Progression of AD Pathomechanism of Alzheimer’s Disease Over a decade earlier of initial symptoms Continuously & Endlessly produced Neuronal death

Aggregation Deposition Amyloid Precursor Protein Neuronal & Synaptic dysfunction Cholinergic Neurons (hippocampus) Inflammation Incipient Stage of AD Irreversible Progression of AD Therapeutic Strategies of Alzheimer’s Disease Neuronal death Neprilysin Activation, etc Secretase Inhibitor/ Modifier Anti-Tau Drug Anti-inflammatory Drug Stem Cell Implant Aggregation Inhibitor Tau protein (NFT) Donepezil, etc

blood Capillaries parenchyma CAA :amyloid angiopathy BBB : Blood-brain barrier BCSFB : Blood-CSF barrier Complexity of Alzheimer’s disease APP :amyloid predursor protein AD :Alzheimer’s disease

RAD = ∑ ( RAPP + RPSEN1 + RPSEN2 + RAPOE + Rn….) + ∑( RENVIR ) + ∑Mod Disease = Genetic causes + Environmental causes + Modifiers Altered Tau metabolism NFT Neuronal dysfunction, Neuronal cell death Dementia Neuronal Injury

New Therapy Early Diagnosis / Early Intervention Mild Moderate ~ Severe Asymptomatic Phase Education, Town Planning, Intergenerational Co-operation Medical Intervention Neuronal Dysfunction / Death Chronic Inflammation Tau Protein Deposition Synaptic Dysfunction Amyloid Deposition Pathological Conditions in AD Brain Don’t stop!! Social challenges for keeping brain healthy

MCI Brain Aging Dementia AD, VD, DLB, FTD etc Brain Ageing, MCI, Dementia Risk Factors Risk Factors Conventional Aspects Therapeutic Intervention

Various Aspects of Brain Aging MCI Paradigm Shift !? Dementia Amyloid Atherosclerosis Endocrine System CSF System Tau Protein Glial cells Neuronal Cell Synuclein Lipid Metabolism Mitochondria Function ER function Synapse Sugar Metabolism Brain Ageing, MCI, Dementia