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635 articles

Concepts

The connective tissue of the corpus — every idea the theses and the vault hold in common. 635 are linked from at least one page and indexed below; 0 orphan notes that nothing yet links to are pooled at the foot.

The load-bearing concepts most referenced

Autophagy

Cellular Senescence

Neuroinflammation

Reelin-ApoE receptor axis disruption

Lysosomal Acidification

PANTHOS

Tau Propagation

cognitive resilience

Autophagic Collapse

Cholesterol Homeostasis

Tau Pathology

Adrenergic Signaling

A 87

Abeta aggregation as necessary initiating event10 Abeta as molecular prime mover2 Abeta as physiological modulator of synaptic homeostasis4 Abeta as stress response marker4 Activated microglia imaging for treatment guidance3 Acyloxyacyl Hydrolase Neuroprotection5 AD as a double prion disorder5 AD as accelerated aging of Abeta management3 AD as accelerated normal aging3 AD as accumulation of insults exceeding homeostasis4 AD as addiction-like circuit pathology3 AD as autoimmune disorder6 AD as clinical syndrome not disease3 AD as multiple diseases3 AD as systemic disease not limited to brain3 AD caused by APP dysregulation not Abeta per se5 AD-diabetes shared mechanism3 Adrenergic Signaling21 Adult hippocampal neurogenesis restoration8 Adult Neurogenesis9 Age-dependent feedback loops in neurodegeneration8 Age-dependent threshold model5 Age-related immune dysfunction enables neurotropic viruses9 Aging accelerators and decelerators3 Aging as Mechanism3 Aging as root cause of AD4 Aging-epigenetic-genetic interaction3 AI Disease Model Discovery2 AI Neurotherapeutic Discovery6 AI-based early diagnosis5 Alpha-sheet toxicity in disease pathogenesis3 Aluminum as primary environmental cause3 Aluminum driving amyloid production4 Amyloid and tau as secondary byproducts3 Amyloid and tau as secondary phenomena3 Amyloid as age-related phenomenon5 Amyloid as antimicrobial defense8 Amyloid as compensatory mechanism8 Amyloid as defense mechanism against parasites3 Amyloid as downstream secondary3 Amyloid as innate immune defense gone awry3 Amyloid as secondary to synaptic dysfunction3 Amyloid clearance as important as deposition3 Amyloid Clinical Disconnect4 Amyloid Nucleation5 Amyloid plaques as fibrotic scar tissue from BBB repair8 Amyloid structural diversity and toxicity3 Amyloid-beta as innate immune defense5 Anti Ferroptotic Botanicals6 Anti-prion therapeutics as novel drug strategy9 Anti-TNF-alpha therapeutic strategy4 Antibody Target Specificity6 Antimicrobial Defense8 Antimicrobial hypothesis of amyloid11 Antioxidant defense failure6 ApoE isoform-heparin binding differences11 ApoE-centric unified model8 APOE4 Endolysosomal Dysfunction2 APOE4 Pathogen Interaction7 ApoE4 structural vulnerability6 APP and tau pathology linked through transport disruption4 APP as dependence receptor5 APP processing pathway3 Astrocyte network management hypothesis6 Astrocyte-centric AD hypothesis8 Astrocyte-centric AD mechanism7 Astrocyte-driven amyloid buildup4 Asymptomatic AD Phenotyping2 Atherosclerosis as AD driver3 Atherosclerotic obstruction4 ATN biomarker classification system5 ATP depletion as direct trigger of tau pathology3 ATP-chaperone-protein folding axis6 Autoimmune contribution via BBB compromise3 Autoimmune Neurodegeneration4 Autophagic Collapse22 Autophagic Flux11 Autophagy51 Autophagy Dysfunction7 Autophagy-amyloid coupling5 Autophagy-lysosomal failure6 Autophagy-metabolism crosstalk in AD4 Axon initial segment as key disease locus5 Axonal atheroma hypothesis3 Axonal Transport10 Axonal transport failure as unifying mechanism4 Ayurvedic medicine approach3

B 28

Bacterial exudate-driven neurodegeneration8 Barrier dysfunction pathology5 BBB as gatekeeper failure3 BBB breakdown cascade8 BBB degradation and pathogen invasion3 BBB-mediated vascular contribution3 BCG Immune Checkpoint Modulation11 Beta Alanine Neurotransmission5 Bimodal brain (inference vs training)4 BIN1 Autophagic Regulation6 Bioenergetic Collapse16 Bioenergetic defects as early events4 Bioenergetics11 Biogenic amines disrupt cellular translation fidelity4 Biological spintronic sensing4 Biomarker gap in neurology3 Blood-based biomarker discovery3 Blood-based biomarker panels for preclinical detection3 Blood-based lipid and protein module biomarkers9 Brain buoyancy hypothesis3 Brain DNA blueprint is altered in AD neurons5 Brain hemisphere synchronization3 Brain Immune Interface10 Brain Lipid Homeostasis Restoration3 Brain plasticity decline driving AD progression3 Brain structure-function relationships3 Brain-glucose-steal as mechanism of cognitive impairment5 Brain-heart health connection6

C 62

Ca2+-cAMP signaling convergence in neurodegeneration3 Calcium dyshomeostasis as upstream AD mechanism5 Calcium Homeostasis7 Calcium signaling disruption3 Calcium-mediated tauopathy3 Cannabinoid Neuroprotection1 Cannabis as primary environmental AD cause3 Causation pyramid model3 CD74 Microglial Signaling2 CDK3 Cell Cycle Toxicity5 Cellular Identity7 Cellular Senescence44 Cellular Vectors4 Cerebral Self-Management Process3 Childhood experience shaping AD vulnerability3 Cholesterol deficiency driving AD pathology17 Cholesterol Homeostasis22 Cholesterol Transport13 Cholinergic network failure in AD12 Cholinergic neuron vulnerability10 Cholinergic primacy in AD10 Chronic Excitatory Insufficiency15 Chronic intracellular infection model5 Chronic intracellular pathogen-driven neurodegeneration3 Chronic intranasal infection explaining slow AD progression3 Chronic mild hypothermia as AD cause3 Chronic neuroinflammation from infection3 Chronic neuroinflammation from periphery7 Chronobiologic neuroprotection via melatonin7 Circadian disruption as cause not consequence5 Circadian Immune Regulation8 Circadian regulation of glial function5 Clearance failure vs. overproduction3 Cognitive fitness as disease-modifying factor5 Cognitive reserve building9 Cognitive reserve hypothesis7 cognitive resilience24 Cognitive resilience as dynamic protective concept4 Community-based dementia support model3 Compensatory Homeostasis6 Computational AD Subtyping2 Computational disease subtyping3 Computational models of associative memory3 Continuum of senile cognitive decline10 Convergent risk factor pathways3 Convergent signaling through Wnt-PCP-RhoA-ROCK3 Convergent Synaptic Collapse11 Cortisol-driven secretase dysfunction7 Coverage Fraction3 Cranial bone compression causing brain atrophy8 CRISPR-like protein immunity model4 Critique of amyloid dogma3 Critique of mono-causal therapeutics3 Cross Disease Prion Mechanisms5 Cross-disease protein aggregation parallels3 CSF flow dynamics4 Culturally adapted dementia care3 Cumulative axonal defect accumulation8 Cumulative inflammation threshold for neurodegeneration4 Curcumin multi-target action4 Cytoskeletal disorder as core pathology5 Cytoskeletal Dynamics7

D 17

Dark Genome Variation11 Dehydration as AD risk factor3 Denervation supersensitivity4 Destructive emotions as root cause of all disease8 Dietary Fatty Acid APOE4 Rescue3 Dietary intervention as primary prevention5 Dietary neuroprotection3 Dietary neurotoxin exposure as modifiable risk factor6 Dietary Sodium Neurodegeneration6 Disease as behavioral feedback mechanism5 Disorientation vs memory loss distinction4 Dose-dependent mitochondrial dysfunction determines pathology type6 Double-hit mutation hypothesis6 Dual Pathogen AD Pathogenesis5 Dynamic and region-independent disease mechanisms9 Dynamic neural circuit failure model8 Dysregulated homeostatic units6

E 43

Early-life neuroinflammatory priming8 ECM remodeling in neurodegeneration6 Eight factors of dementia framework3 Electrochemical basis of cognitive decline3 Emotional transformation as therapeutic approach3 Endocrine-circadian-inflammation axis3 Endolysosomal Dysfunction8 Endosomal Lysosomal Network6 Endosomal Trafficking15 Energy failure as primary AD driver3 Energy failure as root cause3 Energy Metabolism6 Energy metabolism decline3 Energy metabolism failure drives neurodegeneration3 Entropy acceleration from maladaptive thinking6 Entropy as organizing principle10 Environmental and emotional risk factors3 Environmental and socioeconomic risk factors3 Environmental CxI inhibitors as AD etiological agents4 Environmental neurotoxicology3 Environmental Toxicology3 Environmental toxicology of neurodegeneration3 Environmental toxin contribution3 Environmental vs. genetic causation3 Epidemiological correlation argument5 Epigenetic and genetic interplay4 Epigenetic Regulation5 Epigenetic regulation of AD genes3 Epigenetic Repression5 Equilibrium at criticality5 ER Stress10 ESCRT III Membrane Scission6 Evolutionary biochemistry of disease3 Evolutionary framework for AD causation3 Evolutionary mismatch between genes and modern lifestyle14 Evolutionary mismatch hypothesis6 Evolutionary vulnerability of brain structures3 Excitatory Neurotransmission4 Exercise as cognitive catalyst6 Existing HIV RT inhibitors as potential AD therapeutics5 Expanded Prion Paradigm6 Exponential exposure-prevalence correlation3 Extracellular Matrix Pathology3

F 9

Factor classification and connectivity6 Familial vs sporadic AD4 Ferroptosis15 Ferroptosis as implicated pathway11 Ferroptosis in Neurodegeneration10 Ferroptosis Phase II Oligodendrocyte10 Five-factor quintet model of AD causation3 Folate-B12 therapeutic intervention3 Functional model of neuron-glia interaction3

G 27

GAG-driven AD pathogenesis3 Gene dosage of APP directly causes pathogenesis4 Gene Environment Interaction6 Genetic evidence as gold standard for causality6 Genetic shortcuts in FAD vs LOAD3 GI-tract microbiome neurotoxicity8 Glia-neuron interaction dysfunction3 Glial Biology2 Glial contribution to neurodegeneration3 Glial inflammatory response3 Glial-driven neuroinflammatory disease model3 Gliotransmitter dysregulation3 Glycobiology3 Glycolysis-fat oxidation metabolic switch10 Glymphatic Clearance6 Glymphatic clearance failure8 Glymphatic clearance failure amplifies pathology9 GlyNAC as novel nutritional therapeutic for AD4 Gravity and cerebral perfusion4 Gravity-dependent brain perfusion4 Gravity-dependent brain vulnerability4 GSH deficiency as root cause of multiple AD defects7 Gut Brain Axis6 Gut Microbiome Lipid AD Axis8 Gut-brain axis in AD3 Gut-brain axis in neuroinflammation3 Gut-brain axis via tryptamine production4

H 10

Head-down time and dementia3 Head-down time hypothesis3 Health disparities in AD4 Hippocampal hyperexcitability as pre-AD state3 Hippocampal neuron vulnerability3 Holistic multi-level therapeutic approach3 Homeostatic disruption model of AD2 Homeostatic Microglial Collapse12 Host Defense Peptides5 Human-germ interaction model6

I 35

Iatrogenic contribution via medications3 IDE-insulin-Abeta competition10 Immediate preventive interventions4 Immune Checkpoint Therapy11 Immune-pathogen interaction model6 Immunometabolic Checkpoints7 Immunometabolism7 Immunosenescence as central aging mechanism3 Inciting injury model3 Infection as co-factor in neurodegeneration3 Infection-triggered epigenetic cascade model3 Infectious etiology of AD2 Infectious etiology of late-onset AD7 Infectious etiology of LOAD3 Infectious origin of Alzheimer's disease3 Infectious-toxic-genetic synergy3 Inflamm-aging as disease driver6 Inflammaging integrates hallmarks of aging7 Information Theoretic Transcriptomics6 Innate immune function of amyloid proteins3 Innate immune-mediated plaque formation3 Innate Immunity19 Innate immunity failure in sporadic AD5 Innate immunity network dysregulation in AD3 Inside Out Plaque18 Integrated molecular-to-network perspective3 Integrative complementary therapy approach8 Integrative treatment across medical traditions8 Interconnected homeostatic disruption3 Interlinked pathological cascades3 Intracellular Amyloid9 Intraneuronal amyloid accumulation as primary event8 Iron Brain Paradox3 Iron Dyshomeostasis4 iron dyshomeostasis in AD3

K 2

Ketogenic diet as primary AD therapy4 Kinase Inhibitor Neuroprotection5

L 25

L-type CCB neuroprotective strategy8 LC Morphology What is Established7 Lifestyle and behavioral factors5 Lifestyle as causal anchor10 Lifestyle intervention for cognitive reversal3 Lifestyle intervention for neurodegeneration3 Lifestyle Microglial Modulation5 Lifestyle-based AD prevention5 Limbic brain as circavital clock locus5 Lipid Dysregulation3 Lipid homeostasis as AD driver3 Lipid Metabolism10 Lipid Peroxidation12 Lipid peroxidation cascade at synapse12 Lipid Transport8 Lipid-driven neurodegeneration3 Lipid-glycan crosstalk in AD5 Liver-brain metabolic axis3 Lock and Key memory reactivation7 Locus coeruleus as ground zero12 Long preclinical phase of AD pathology5 Longitudinal observational evidence5 Lysosomal Acidification32 Lysosomal Dysfunction18 Lysosomal Storage Disease4

M 61

Matrix Sulfation Node11 Mechanical risk factor for AD3 Meditation as neuroprotective intervention6 Membrane Biology3 Membrane Biophysics8 Membrane Lipid Dysregulation2 Membrane lipid pathology in AD3 Memory building framework4 Memory construction disease model3 Memory encoding-retrieval interference3 Meningeal T Cell Regulation8 Mercury as primary AD cause4 Metabolic dysfunction as AD driver3 Metabolic dysfunction in neurodegeneration3 Metabolic origin of amyloid and tau3 Metabolic-neurodegenerative disease axis3 Metabolic-neurodegenerative disease connection4 Metal-protein interaction in disease3 Microbial Pathogenesis5 Microbiome-immune-brain integration10 Microbleeds as initiating vascular event in AD5 Microglial cytokine storm10 Microglial dysfunction as early event3 Microglial Immunometabolism2 Microglial Lipid Regulation2 Microglial Protein Biomarkers10 Microglial senescence as AD trigger10 Micronutrient therapeutic potential3 Microtubule quantum information processing7 Mind-body causation in neurodegeneration3 Mind-body correspondence in disease formation3 Mind-body-soul integration for treatment7 miRNA as mechanistic link3 Mitochondrial Dysfunction21 Mitochondrial inheritance and AD3 Mitochondrial theory of aging4 Modifiability of AD risk6 Modifiable risk factor intervention5 Morphological analysis methodology12 Mosaic model of aging brain6 Moving brain hypothesis5 MTHFR as catalytic pre-existing factor8 Multi-cellular pathology6 Multi-factorial etiology of AD3 Multi-level heterogeneity of AD3 Multi-omics network approach to AD3 Multi-pathway AD pathophysiology review4 Multi-system medicine approach to AD3 Multi-target vs mono-target3 Multi-targeting the amyloid hypothesis3 Multidomain AD Intervention6 Multifactorial causal network3 Multifactorial convergence model3 Multifactorial etiology3 Multifactorial modulation of disease trajectory5 Multifactorial prevention through modifiable risk factors6 Multifactorial risk accumulation model3 Multipathology convergence theory3 Multiple chronic stressors3 Multiple converging factors in unified tauopathy framework4 Musical reminiscence as neurological intervention3

N 38

NAD+ depletion drives neurodegeneration3 Natural product polytherapy3 Navigable database of AD factors3 NbM as origin of sporadic AD3 Necrotic Cell Death4 Need to understand normal APP function5 Network-based combination therapy6 Network-based neurodegeneration3 Neural circuit breakdown model4 Neural Oscillations3 Neurodegeneration as aberrant development5 Neuroendocrine shift at menopause4 Neuroimmune Surveillance11 Neuroimmunology9 Neuroinflammation39 Neuroinflammation as primary driver connecting all AD subsystems3 Neuroinflammatory disequilibrium4 Neuronal activity as survival factor5 Neuronal Excitability4 Neuronal lysis forming extracellular plaques8 Neuronal maturation context in disease3 Neuronal network degradation as substrate of dementia5 Neuroplasticity-based cognitive enhancement4 Neurotransmitter disruption cascade3 Neurovascular dysfunction as initiating event12 Neurovascular injury-repair cycle driving disease progression10 Neurovascular unit as disease origin8 NF-kB-miRNA inflammatory cascade5 Non-dimensional quantum pathway3 Non-enzymatic AChE signaling6 Non-invasive thermal therapy3 Non-optimal aging rather than normal aging process3 Non-pharmacological cognitive enhancement3 Novel systems analysis approach3 Nuclear pathology as early AD mechanism8 Nutritional deficiency as AD cause5 Nutritional modulation of neuroinflammation3 Nutritional rebalancing over pharmacological intervention3

O 17

Olfactory Route Neuroinvasion7 Olfactory vector hypothesis9 Oligomer hypothesis of neurotoxicity6 Omics Driven Profiling2 Omnigenic AD architecture5 Onset vs Progression6 Oral Microbiome5 Oral-brain infection axis3 Oskar Fischer Founder21 Oxidative and nitrative stress as primary driver3 Oxidative Stress13 Oxidative stress and apoptosis pathways4 Oxidative stress as trigger3 Oxidative stress as unifying mechanism4 Oxygen as fundamental homeostatic mediator3 Oxygen deficiency as root cause6 Oxygenation-based therapeutic approach2

P 53

P. gingivalis as keystone pathogen5 PANTHOS25 Parasitic mite infestation as AD cause3 Pathogen Driven Neurodegeneration2 Pathogen-specific AD subtypes5 Pathological supersystem model3 Peptide Neurotherapeutics5 Perineuronal Nets21 Peripheral Immunocyte Regulation4 Peripheral Lipid Biomarkers6 PERK DLX1 Tau Axis5 Peroxidized ApoE as proximate cause11 Peroxynitrite-mediated neurodegeneration3 Personalized multifactorial etiology4 Phagocytic Clearance9 Pharmacological neuroprotection3 Phase Measurability12 Physics of organisms approach4 Plaque IgG Sequestration7 Plaque Origin What is Established21 Plaque-cognition dissociation7 Polymicrobial brain infection2 Polymicrobial causation of AD3 Polytherapeutic natural product approach3 Population-specific AD genetic signatures3 Post-translational modification as prion trigger4 Post-translational modification dysregulation7 Precision genomics approach3 Precision Medicine AD5 Precision medicine approach3 Precision medicine for AD3 Precision medicine protocol6 Preclinical Phase Activity5 Presymptomatic Lipidomic Signatures2 Prion infectivity distinct from insoluble protein accumulation5 Prion-like disease propagation17 Probabilistic multi-cause disease etiology3 Production-clearance equilibrium5 Programmed aging clock model of AD3 Proteasome Tau Feedback13 Protein biosynthesis interference as root cause4 Protein denaturation as disease driver3 Protein Misfolding7 Protein templating and seeding9 Proteoglycan role in amyloid formation6 Proteostasis15 Proteostasis Collapse3 Proteostasis disruption5 Psychological origins of neurodegeneration4 Psychology as primary disease trigger3 Psychosocial Risk Factors4 Psychosomatic cascade to neurodegeneration3 Psychosomatic model of Alzheimer's disease3

Q 2

Quality Control Collapse10 Quantum consciousness in neurons3

R 17

Reasoning-numerical cognitive separation6 Receptor-based therapeutic approach3 Receptor-mediated amyloid internalization6 Redox chemistry therapeutic approach3 Redox signaling as central mechanism3 Reelin-ApoE receptor axis disruption34 Region-selective neuronal vulnerability8 Repurposing antihypertensives for AD3 Resilience as key to understanding AD clinical expression3 Retrogenesis model4 Retrotransposon Activation5 Retroviral-like mechanisms drive disease propagation17 Revisiting failed drug trials3 Risk factor convergence3 RNA-based diagnostics and therapeutics5 ROS-calcium signaling axis3 Runaway synaptic modification hypothesis3

S 53

Selective Tau Disruption4 selective vulnerability of PV interneurons1 Self-DMN dysfunction hypothesis3 Sense-making failure and cellular conflict6 Sensory Loss Dementia Correlation4 Sex Differences in Tauopathy2 Sex Dimorphic AD Mechanisms3 Sex Specific MiRNA Signatures3 Sex-based hemoglobin differential3 Sex-specific AD vulnerability3 Sex-specific disease mechanisms5 Sigma-1 receptor-mediated neuroprotection3 Signal Insufficiency Model (SIM)10 Silica water as protective intervention4 Single Cell AD Signatures5 Sinus-brain barrier breach enabling neurodegeneration4 SIRT1 neuroprotection3 Sleep position and brain maintenance3 Sleep posture and brain maintenance3 Sleep timing and gravitational stretching7 Sleep-AD connection4 Small molecule polypharmacology3 Small ncRNA regulation of neurodegeneration5 Solar gravitational muscle constriction theory6 Somatic Mosaicism in AD9 Somatic mutations as novel therapeutic targets8 Somatic recombination creates pathogenic gene variants21 SORL1 Lysosomal Function6 SorLA Lipid ER Regulation6 Sphingolipid Signaling5 Spiritual and karmic etiology3 SSRI repurposing for neurodegeneration3 Staged anatomical progression5 Substance abuse and neurodegeneration7 Sundowner symptoms from evening muscle constriction5 SuperAgers demonstrate pathology-cognition dissociation5 Synapse loss as primary event3 Synaptic Competition5 Synaptic dysfunction as primary driver3 Synaptic impairment as primary pathomechanism3 Synaptic Pathology13 Synaptic Physiology2 Synaptic Plasticity12 Synaptic plasticity failure3 Synaptoblastic vs synaptoclastic balance5 Syndromic Complexity3 Systemic circulating factors governing neurodegeneration4 Systemic disease beyond CNS3 Systemic disease interaction model3 Systemic to Central Immune Signaling3 Systems approach to interconnected AD pathological hallmarks3 Systems Biology9 Systems thinking and feedback loops3

T 31

T14 feedforward toxicity cascade5 T14 Toxin Antagonism7 Tau as conditional prion9 Tau as primary causative factor over amyloid3 Tau Biomarkers9 Tau Pathology22 Tau prions drive disease more than Abeta prions5 Tau Propagation25 Tau Scaffolding Interactions5 Tauopathy primacy over amyloidopathy5 Tauopathy Sleep Disruption2 Temperature-dependent protein misfolding5 Terminal thoughts and genetic change3 Theoretical brain cognition framework3 Theory integration across domains7 Three-actor-group pathogenesis3 Threshold and set point model for neurodegeneration3 TNF-alpha as central AD mediator3 TOMM40 Import Gate21 Torsion field theory of AD3 Toxic Abeta species and PTMs3 Traditional medicine integration4 Trained Immunity8 Transcriptional Pause Release7 Transcriptomic Isoform Complexity8 Translational Regulation in Tauopathy5 Transsulfuration pathway dysfunction4 Transsynaptic tau propagation13 Trauma Induced Viral Reactivation6 TXNIP as therapeutic target3 Type 2 diabetes as AD risk factor3

U 2

Understanding Abeta function key to early identification4 Unified theory of AD etiology5

V 13

Vascular Amyloid Interaction5 Vascular and inflammatory contributions3 Vascular dysfunction as earliest detectable change3 Vascular insufficiency hypothesis5 Vascular-mechanical etiology3 Vascular-metabolic-infectious convergence3 Vascular-sleep interaction3 Vesicular Trafficking7 Vessel Associated Microglial Activation9 Viral infection triggers chronic brain inflammation3 Viral Pathogenesis3 Viral trigger hypothesis for neurodegeneration3 Vitamin E-miRNA-inflammation axis5

W 2

Wear and tear accumulation3 Wnt-GSK3-beta pathway integrating amyloid and tau pathology3

Z 1

Zeitgeber-driven neurodegeneration3

Discussion

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