634 articles

Concepts

The connective tissue of the corpus — every idea the theses and the vault hold in common. 545 are linked from at least one page and indexed below; 89 orphan notes that nothing yet links to are pooled at the foot.

The load-bearing concepts most referenced

Concept13 refs

Inside Out Plaque

A 72

Abeta aggregation as necessary initiating event2 Abeta as stress response marker1 Activated microglia imaging for treatment guidance1 Acyloxyacyl Hydrolase Neuroprotection· AD as accelerated aging of Abeta management· AD as accelerated normal aging· AD as accumulation of insults exceeding homeostasis· AD as addiction-like circuit pathology2 AD as autoimmune disorder· AD as clinical syndrome not disease1 AD as multiple diseases· AD as systemic disease not limited to brain· AD-diabetes shared mechanism· Adrenergic Signaling2 Adult hippocampal neurogenesis restoration6 Adult Neurogenesis4 Age-dependent threshold model1 Age-related immune dysfunction enables neurotropic viruses· Aging accelerators and decelerators· Aging as Mechanism1 Aging as root cause of AD1 Aging-epigenetic-genetic interaction· AI Neurotherapeutic Discovery· AI-based early diagnosis1 Alpha-sheet toxicity in disease pathogenesis· Aluminum as primary environmental cause· Aluminum driving amyloid production2 Amyloid and tau as secondary byproducts· Amyloid and tau as secondary phenomena· Amyloid as age-related phenomenon· Amyloid as antimicrobial defense2 Amyloid as compensatory mechanism1 Amyloid as downstream secondary· Amyloid as innate immune defense gone awry· Amyloid as secondary to synaptic dysfunction· Amyloid clearance as important as deposition1 Amyloid Nucleation1 Amyloid plaques as fibrotic scar tissue from BBB repair1 Amyloid structural diversity and toxicity· Amyloid-beta as innate immune defense1 Anti Ferroptotic Botanicals2 Anti-prion therapeutics as novel drug strategy1 Anti-TNF-alpha therapeutic strategy1 Antibody Target Specificity1 Antimicrobial Defense1 Antimicrobial hypothesis of amyloid1 Antioxidant defense failure1 ApoE isoform-heparin binding differences6 ApoE4 structural vulnerability· APP and tau pathology linked through transport disruption· APP processing pathway· Astrocyte network management hypothesis1 Astrocyte-centric AD hypothesis1 Astrocyte-centric AD mechanism1 Astrocyte-driven amyloid buildup1 Atherosclerotic obstruction1 ATN biomarker classification system1 ATP depletion as direct trigger of tau pathology1 ATP-chaperone-protein folding axis1 Autoimmune contribution via BBB compromise· Autoimmune Neurodegeneration· Autophagic Collapse4 Autophagic Flux1 Autophagy1 Autophagy Dysfunction· Autophagy-amyloid coupling1 Autophagy-lysosomal failure1 Autophagy-metabolism crosstalk in AD· Axonal atheroma hypothesis· Axonal Transport· Axonal transport failure as unifying mechanism· Ayurvedic medicine approach·

B 24

Barrier dysfunction pathology2 BBB as gatekeeper failure· BBB breakdown cascade1 BBB degradation and pathogen invasion3 BBB-mediated vascular contribution· BCG Immune Checkpoint Modulation2 Bimodal brain (inference vs training)1 BIN1 Autophagic Regulation1 Bioenergetic defects as early events· Bioenergetics7 Biogenic amines disrupt cellular translation fidelity· Biological spintronic sensing· Biomarker gap in neurology· Blood-based biomarker discovery· Blood-based biomarker panels for preclinical detection1 Blood-based lipid and protein module biomarkers1 Brain buoyancy hypothesis· Brain hemisphere synchronization· Brain Immune Interface2 Brain Lipid Homeostasis Restoration2 Brain plasticity decline driving AD progression· Brain structure-function relationships· Brain-glucose-steal as mechanism of cognitive impairment· Brain-heart health connection1

C 56

Ca2+-cAMP signaling convergence in neurodegeneration· Calcium dyshomeostasis as upstream AD mechanism· Calcium Homeostasis· Calcium-mediated tauopathy· Cannabis as primary environmental AD cause· Causation pyramid model· CD74 Microglial Signaling· CDK3 Cell Cycle Toxicity· Cellular Identity2 Cellular Senescence9 Cellular Vectors· Cerebral Self-Management Process2 Childhood experience shaping AD vulnerability· Cholesterol deficiency driving AD pathology4 Cholesterol Homeostasis2 Cholesterol Transport2 Cholinergic network failure in AD3 Cholinergic neuron vulnerability3 Cholinergic primacy in AD4 Chronic intracellular pathogen-driven neurodegeneration· Chronic mild hypothermia as AD cause· Chronic neuroinflammation from infection· Chronic neuroinflammation from periphery1 Chronobiologic neuroprotection via melatonin2 Circadian disruption as cause not consequence2 Circadian Immune Regulation2 Circadian regulation of glial function2 Clearance failure vs. overproduction· Cognitive fitness as disease-modifying factor· Cognitive reserve building1 Cognitive reserve hypothesis1 cognitive resilience5 Cognitive resilience as dynamic protective concept6 Community-based dementia support model· Compensatory Homeostasis1 Computational disease subtyping· Computational models of associative memory· Continuum of senile cognitive decline2 Convergent risk factor pathways· Convergent signaling through Wnt-PCP-RhoA-ROCK· Convergent Synaptic Collapse1 Cortisol-driven secretase dysfunction2 Coverage Fraction2 Cranial bone compression causing brain atrophy· CRISPR-like protein immunity model· Critique of amyloid dogma· Critique of mono-causal therapeutics· Cross Disease Prion Mechanisms· Cross-disease protein aggregation parallels· CSF flow dynamics· Culturally adapted dementia care· Cumulative axonal defect accumulation· Cumulative inflammation threshold for neurodegeneration7 Curcumin multi-target action· Cytoskeletal disorder as core pathology2 Cytoskeletal Dynamics1

D 17

Dark Genome Variation3 Dehydration as AD risk factor· Denervation supersensitivity· Destructive emotions as root cause of all disease2 Dietary Fatty Acid APOE4 Rescue1 Dietary intervention as primary prevention· Dietary neuroprotection· Dietary neurotoxin exposure as modifiable risk factor2 Dietary Sodium Neurodegeneration· Disease as behavioral feedback mechanism· Disorientation vs memory loss distinction· Dose-dependent mitochondrial dysfunction determines pathology type1 Double-hit mutation hypothesis3 Dual Pathogen AD Pathogenesis· Dynamic and region-independent disease mechanisms· Dynamic neural circuit failure model2 Dysregulated homeostatic units1

E 38

Early-life neuroinflammatory priming3 ECM remodeling in neurodegeneration1 Eight factors of dementia framework· Electrochemical basis of cognitive decline· Emotional transformation as therapeutic approach· Endocrine-circadian-inflammation axis· Endolysosomal Dysfunction· Endosomal Lysosomal Network3 Endosomal Trafficking4 Energy failure as primary AD driver· Energy failure as root cause· Energy Metabolism· Energy metabolism decline· Energy metabolism failure drives neurodegeneration· Entropy acceleration from maladaptive thinking· Environmental and emotional risk factors· Environmental and socioeconomic risk factors· Environmental CxI inhibitors as AD etiological agents1 Environmental Toxicology· Environmental toxicology of neurodegeneration· Environmental toxin contribution· Environmental vs. genetic causation· Epidemiological correlation argument· Epigenetic and genetic interplay· Epigenetic Regulation· Epigenetic regulation of AD genes· ER Stress· ESCRT III Membrane Scission· Evolutionary biochemistry of disease· Evolutionary framework for AD causation· Evolutionary mismatch between genes and modern lifestyle1 Evolutionary vulnerability of brain structures· Excitatory Neurotransmission4 Exercise as cognitive catalyst3 Existing HIV RT inhibitors as potential AD therapeutics3 Expanded Prion Paradigm· Exponential exposure-prevalence correlation· Extracellular Matrix Pathology·

F 9

Factor classification and connectivity1 Familial vs sporadic AD3 Ferroptosis4 Ferroptosis as implicated pathway4 Ferroptosis in Neurodegeneration4 Ferroptosis Phase II Oligodendrocyte7 Five-factor quintet model of AD causation· Folate-B12 therapeutic intervention· Functional model of neuron-glia interaction·

G 23

Gene dosage of APP directly causes pathogenesis1 Gene Environment Interaction2 Genetic shortcuts in FAD vs LOAD· GI-tract microbiome neurotoxicity1 Glial Biology· Glial contribution to neurodegeneration· Glial inflammatory response· Glial-driven neuroinflammatory disease model· Gliotransmitter dysregulation· Glycobiology· Glycolysis-fat oxidation metabolic switch2 Glymphatic Clearance1 Glymphatic clearance failure1 Glymphatic clearance failure amplifies pathology2 GlyNAC as novel nutritional therapeutic for AD· Gravity and cerebral perfusion3 Gravity-dependent brain perfusion1 Gravity-dependent brain vulnerability1 GSH deficiency as root cause of multiple AD defects1 Gut Brain Axis· Gut Microbiome Lipid AD Axis1 Gut-brain axis in neuroinflammation· Gut-brain axis via tryptamine production2

H 6

Health disparities in AD· Hippocampal neuron vulnerability· Holistic multi-level therapeutic approach· Homeostatic disruption model of AD· Homeostatic Microglial Collapse1 Host Defense Peptides·

I 33

Iatrogenic contribution via medications· IDE-insulin-Abeta competition· Immediate preventive interventions1 Immune Checkpoint Therapy1 Immunometabolic Checkpoints1 Immunometabolism· Immunosenescence as central aging mechanism· Inciting injury model· Infection as co-factor in neurodegeneration· Infection-triggered epigenetic cascade model· Infectious etiology of AD· Infectious etiology of late-onset AD1 Infectious etiology of LOAD· Infectious origin of Alzheimer's disease· Infectious-toxic-genetic synergy· Inflamm-aging as disease driver3 Inflammaging integrates hallmarks of aging1 Information Theoretic Transcriptomics1 Innate immune function of amyloid proteins· Innate immune-mediated plaque formation· Innate Immunity· Innate immunity failure in sporadic AD1 Innate immunity network dysregulation in AD· Inside Out Plaque6 Integrated molecular-to-network perspective· Integrative complementary therapy approach· Integrative treatment across medical traditions1 Interconnected homeostatic disruption· Intracellular Amyloid3 Intraneuronal amyloid accumulation as primary event· Iron Brain Paradox1 Iron Dyshomeostasis· iron dyshomeostasis in AD1

K 2

Ketogenic diet as primary AD therapy· Kinase Inhibitor Neuroprotection9

L 25

L-type CCB neuroprotective strategy2 LC Morphology What is Established2 Lifestyle and behavioral factors· Lifestyle as causal anchor3 Lifestyle intervention for cognitive reversal· Lifestyle intervention for neurodegeneration· Lifestyle Microglial Modulation· Lifestyle-based AD prevention· Limbic brain as circavital clock locus· Lipid Dysregulation· Lipid homeostasis as AD driver· Lipid Metabolism· Lipid Peroxidation2 Lipid peroxidation cascade at synapse5 Lipid Transport· Lipid-driven neurodegeneration· Lipid-glycan crosstalk in AD1 Liver-brain metabolic axis· Lock and Key memory reactivation1 Locus coeruleus as ground zero2 Long preclinical phase of AD pathology1 Longitudinal observational evidence1 Lysosomal Acidification1 Lysosomal Dysfunction· Lysosomal Storage Disease·

M 51

Matrix Sulfation Node2 Mechanical risk factor for AD· Meditation as neuroprotective intervention1 Membrane Biology· Membrane Biophysics· Membrane Lipid Dysregulation· Membrane lipid pathology in AD· Memory building framework· Memory construction disease model· Memory encoding-retrieval interference· Meningeal T Cell Regulation2 Mercury as primary AD cause· Metabolic dysfunction as AD driver· Metabolic dysfunction in neurodegeneration· Metabolic origin of amyloid and tau· Metabolic-neurodegenerative disease connection1 Metal-protein interaction in disease· Microbial Pathogenesis2 Microbiome-immune-brain integration3 Microglial cytokine storm4 Microglial dysfunction as early event· Microglial Immunometabolism· Microglial Protein Biomarkers· Microglial senescence as AD trigger5 Micronutrient therapeutic potential1 Microtubule quantum information processing2 Mind-body causation in neurodegeneration· Mind-body correspondence in disease formation· Mind-body-soul integration for treatment2 miRNA as mechanistic link· Mitochondrial Dysfunction2 Mitochondrial inheritance and AD· Mitochondrial theory of aging1 Modifiable risk factor intervention1 MTHFR as catalytic pre-existing factor1 Multi-factorial etiology of AD· Multi-level heterogeneity of AD· Multi-omics network approach to AD· Multi-pathway AD pathophysiology review· Multi-system medicine approach to AD· Multi-targeting the amyloid hypothesis· Multidomain AD Intervention· Multifactorial causal network· Multifactorial convergence model· Multifactorial etiology· Multifactorial modulation of disease trajectory1 Multifactorial prevention through modifiable risk factors1 Multipathology convergence theory· Multiple chronic stressors· Multiple converging factors in unified tauopathy framework· Musical reminiscence as neurological intervention·

N 34

NAD+ depletion drives neurodegeneration· Natural product polytherapy· Navigable database of AD factors· NbM as origin of sporadic AD1 Necrotic Cell Death· Network-based combination therapy2 Network-based neurodegeneration· Neural circuit breakdown model2 Neural Oscillations2 Neuroendocrine shift at menopause· Neuroimmune Surveillance2 Neuroimmunology· Neuroinflammation1 Neuroinflammation as primary driver connecting all AD subsystems· Neuroinflammatory disequilibrium1 Neuronal activity as survival factor1 Neuronal Excitability· Neuronal lysis forming extracellular plaques4 Neuronal maturation context in disease· Neuronal network degradation as substrate of dementia2 Neuroplasticity-based cognitive enhancement· Neurotransmitter disruption cascade· Neurovascular dysfunction as initiating event2 Neurovascular injury-repair cycle driving disease progression4 Neurovascular unit as disease origin2 Non-dimensional quantum pathway· Non-invasive thermal therapy· Non-optimal aging rather than normal aging process· Non-pharmacological cognitive enhancement· Novel systems analysis approach· Nuclear pathology as early AD mechanism1 Nutritional deficiency as AD cause1 Nutritional modulation of neuroinflammation· Nutritional rebalancing over pharmacological intervention2

O 13

Olfactory Route Neuroinvasion· Olfactory vector hypothesis1 Oligomer hypothesis of neurotoxicity· Onset vs Progression· Oral Microbiome1 Oral-brain infection axis· Oskar Fischer Founder9 Oxidative and nitrative stress as primary driver· Oxidative Stress· Oxidative stress as unifying mechanism· Oxygen as fundamental homeostatic mediator· Oxygen deficiency as root cause1 Oxygenation-based therapeutic approach·

P 45

P. gingivalis as keystone pathogen1 PANTHOS6 Pathogen Driven Neurodegeneration· Pathogen-specific AD subtypes· Pathological supersystem model· Peptide Neurotherapeutics1 Perineuronal Nets13 Peripheral Immunocyte Regulation2 Peripheral Lipid Biomarkers2 PERK DLX1 Tau Axis· Peroxidized ApoE as proximate cause1 Peroxynitrite-mediated neurodegeneration· Personalized multifactorial etiology· Phagocytic Clearance1 Phase Measurability5 Physics of organisms approach· Plaque IgG Sequestration1 Plaque Origin What is Established5 Plaque-cognition dissociation· Polymicrobial brain infection· Polymicrobial causation of AD· Population-specific AD genetic signatures· Post-translational modification as prion trigger· Precision genomics approach· Precision Medicine AD· Precision medicine approach· Precision medicine for AD· Preclinical Phase Activity1 Prion-like disease propagation4 Probabilistic multi-cause disease etiology· Production-clearance equilibrium1 Programmed aging clock model of AD· Proteasome Tau Feedback· Protein biosynthesis interference as root cause1 Protein denaturation as disease driver· Protein Misfolding· Protein templating and seeding3 Proteoglycan role in amyloid formation1 Proteostasis· Proteostasis Collapse· Proteostasis disruption· Psychological origins of neurodegeneration· Psychology as primary disease trigger· Psychosomatic cascade to neurodegeneration· Psychosomatic model of Alzheimer's disease·

Q 2

Quality Control Collapse· Quantum consciousness in neurons·

R 15

Reasoning-numerical cognitive separation1 Receptor-based therapeutic approach· Receptor-mediated amyloid internalization1 Redox chemistry therapeutic approach· Redox signaling as central mechanism· Reelin-ApoE receptor axis disruption9 Region-selective neuronal vulnerability2 Repurposing antihypertensives for AD· Resilience as key to understanding AD clinical expression4 Retrogenesis model· Retroviral-like mechanisms drive disease propagation1 Revisiting failed drug trials1 Risk factor convergence· ROS-calcium signaling axis· Runaway synaptic modification hypothesis·

S 44

Selective Tau Disruption1 selective vulnerability of PV interneurons5 Self-DMN dysfunction hypothesis· Sense-making failure and cellular conflict· Sensory Loss Dementia Correlation1 Sex Differences in Tauopathy· Sex-based hemoglobin differential1 Sex-specific AD vulnerability· Sigma-1 receptor-mediated neuroprotection· Silica water as protective intervention· Single Cell AD Signatures· Sinus-brain barrier breach enabling neurodegeneration1 SIRT1 neuroprotection· Sleep position and brain maintenance1 Sleep timing and gravitational stretching2 Sleep-AD connection1 Small molecule polypharmacology2 Solar gravitational muscle constriction theory1 Somatic Mosaicism in AD· Somatic mutations as novel therapeutic targets4 Somatic recombination creates pathogenic gene variants3 SORL1 Lysosomal Function· SorLA Lipid ER Regulation· Sphingolipid Signaling2 Spiritual and karmic etiology· SSRI repurposing for neurodegeneration· Staged anatomical progression4 Substance abuse and neurodegeneration· Sundowner symptoms from evening muscle constriction1 Synapse loss as primary event2 Synaptic Competition· Synaptic dysfunction as primary driver· Synaptic impairment as primary pathomechanism· Synaptic Pathology· Synaptic Plasticity· Synaptic plasticity failure· Synaptoblastic vs synaptoclastic balance2 Systemic circulating factors governing neurodegeneration· Systemic disease beyond CNS· Systemic disease interaction model· Systemic to Central Immune Signaling· Systems approach to interconnected AD pathological hallmarks· Systems Biology· Systems thinking and feedback loops1

T 24

T14 Toxin Antagonism· Tau as conditional prion1 Tau as primary causative factor over amyloid· Tau Pathology· Tau Propagation2 Tauopathy primacy over amyloidopathy1 Tauopathy Sleep Disruption· Temperature-dependent protein misfolding· Terminal thoughts and genetic change· Theoretical brain cognition framework1 Theory integration across domains2 Three-actor-group pathogenesis· Threshold and set point model for neurodegeneration1 TNF-alpha as central AD mediator· TOMM40 Import Gate6 Torsion field theory of AD· Toxic Abeta species and PTMs· Trained Immunity· Transcriptional Pause Release· Transcriptomic Isoform Complexity· Translational Regulation in Tauopathy· Transsulfuration pathway dysfunction· Transsynaptic tau propagation1 Trauma Induced Viral Reactivation1

V 10

Vascular Amyloid Interaction· Vascular and inflammatory contributions· Vascular dysfunction as earliest detectable change· Vascular insufficiency hypothesis· Vascular-metabolic-infectious convergence· Vessel Associated Microglial Activation4 Viral infection triggers chronic brain inflammation3 Viral Pathogenesis· Viral trigger hypothesis for neurodegeneration· Vitamin E-miRNA-inflammation axis2

W 1

Wear and tear accumulation·

Z 1

Zeitgeber-driven neurodegeneration·

Loose threads89 unreferenced

Concept notes that no thesis or page currently links to — imported claim-fragments, kept for completeness. They do not yet hold an argument up; when a paper comes to lean on one, it graduates into the index above.

Abeta as molecular prime mover Abeta as physiological modulator of synaptic homeostasis AD as a double prion disorder AD caused by APP dysregulation not Abeta per se Age-dependent feedback loops in neurodegeneration AI Disease Model Discovery Amyloid as defense mechanism against parasites Amyloid Clinical Disconnect ApoE-centric unified model APOE4 Endolysosomal Dysfunction APOE4 Pathogen Interaction APP as dependence receptor Asymptomatic AD Phenotyping Atherosclerosis as AD driver Axon initial segment as key disease locus Bacterial exudate-driven neurodegeneration Beta Alanine Neurotransmission Bioenergetic Collapse Brain DNA blueprint is altered in AD neurons Calcium signaling disruption Cannabinoid Neuroprotection Chronic intracellular infection model Chronic intranasal infection explaining slow AD progression Computational AD Subtyping Entropy as organizing principle Environmental neurotoxicology Epigenetic Repression Equilibrium at criticality Evolutionary mismatch hypothesis GAG-driven AD pathogenesis Genetic evidence as gold standard for causality Glia-neuron interaction dysfunction Gut-brain axis in AD Head-down time and dementia Head-down time hypothesis Hippocampal hyperexcitability as pre-AD state Human-germ interaction model Immune-pathogen interaction model Interlinked pathological cascades Metabolic-neurodegenerative disease axis Microbleeds as initiating vascular event in AD Microglial Lipid Regulation Modifiability of AD risk Morphological analysis methodology Mosaic model of aging brain Moving brain hypothesis Multi-cellular pathology Multi-target vs mono-target Multifactorial risk accumulation model Need to understand normal APP function Neurodegeneration as aberrant development NF-kB-miRNA inflammatory cascade Non-enzymatic AChE signaling Omics Driven Profiling Omnigenic AD architecture Oxidative stress and apoptosis pathways Oxidative stress as trigger Parasitic mite infestation as AD cause Pharmacological neuroprotection Polytherapeutic natural product approach Post-translational modification dysregulation Precision medicine protocol Presymptomatic Lipidomic Signatures Prion infectivity distinct from insoluble protein accumulation Psychosocial Risk Factors Retrotransposon Activation RNA-based diagnostics and therapeutics Sex Dimorphic AD Mechanisms Sex Specific MiRNA Signatures Sex-specific disease mechanisms Signal Insufficiency Model (SIM)Sleep posture and brain maintenance Small ncRNA regulation of neurodegeneration SuperAgers demonstrate pathology-cognition dissociation Synaptic Physiology Syndromic Complexity T14 feedforward toxicity cascade Tau Biomarkers Tau prions drive disease more than Abeta prions Tau Scaffolding Interactions Traditional medicine integration TXNIP as therapeutic target Type 2 diabetes as AD risk factor Understanding Abeta function key to early identification Unified theory of AD etiology Vascular-mechanical etiology Vascular-sleep interaction Vesicular Trafficking Wnt-GSK3-beta pathway integrating amyloid and tau pathology