Alzheimer's disease: an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. Alzheimer's Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What Alzheimer's is Dementia versus Alzheimer's, who it affects, the numbers.
The brain that forgets Where it starts and how it spreads, stage by stage.
Amyloid, animated From one protein cut to a plaque, and the debate about it.
Tau and the tangle How a scaffold protein turns into a tangle and spreads.
Microglia and the lost synapse Inflammation, pruning, and the strongest link to memory loss.
Genes and inheritance APOE, the dominant families, Down syndrome, and what a test means.
Twenty years before symptoms The biomarker cascade, in order.
Stages and symptoms From no symptoms to severe dementia, function by function.
Diagnosis and biomarkers Criteria, scans, spinal fluid, blood tests and screening tools.
The differential Delirium, vascular, Lewy body, frontotemporal and reversible causes.
Cholinesterase inhibitors and memantine Inside the synapse, and what the benefit really is.
Anti-amyloid antibodies over time Lecanemab and donanemab over 18 months, ARIA and the debate.
Beyond memory Agitation, mood, psychosis and sleep, and the drug cautions.
Lowering the risk The 14 modifiable risk factors and what trials show.
Living with dementia and caregiving Planning, safety, caregivers and the end of life.
Nursing care Assessment, giving the medicines, communication, documentation.
Toward a cure The pipeline, prevention trials, and the evidence for each route.
History and people From Auguste Deter in 1901 to the antibodies.
Flashcards and mnemonics Flip cards by topic.
Quiz Questions with explanations.
Glossary Every term, searchable.
Sources Every reference behind the app.

Part 2 · Course and diagnosis

Twenty years before symptoms

Alzheimer's changes in the brain long before anyone notices. Biomarkers turn abnormal in a broadly predictable order: amyloid, then tau and nerve-cell damage, then thinking. Play the clock, and switch between families with a dominant gene and the common late-onset form.

Timeline

Clock

Where is this person on the 2024 map?

In 2024 an Alzheimer's Association workgroup proposed two scales: a biological stage from biomarkers (A to D, by how far tau has spread on PET) and a clinical stage from symptoms (0 to 6). The International Working Group (IWG) disagreed about what to call people without symptoms. Set the biomarkers and symptoms, or pick an example. ^122,255

Examples

Amyloid (Core 1)

Tau PET

Symptoms

Shaded cells: the expected diagonal from 1A to 4–6D. Hatched: no Core 1 biomarker abnormal.

How the model and the definitions changed

Hypothetical model

Jack 2010, revised 2013

The 2010 model put amyloid first and neurodegeneration (CSF tau, MRI atrophy, FDG) after a variable lag, tracking symptoms. The 2013 update indexed people by time, added person-to-person variation, reordered some markers, and proposed that tau may start on its own in sporadic disease and be accelerated by amyloid. ^252,253

Measured

DIAN, and its caveats

DIAN's numbers come from 128 mutation carriers placed on a clock set by the parent's age at onset. Longitudinal data from 217 people confirmed amyloid changes first, but disagreed with the cross-sectional timing of CSF tau by more than 10 years and showed CSF p-tau181 falling near onset. The authors warn the results may not apply to sporadic Alzheimer's. ^41,345

Definitions moved

2011, 2018, 2024

In 2011, diagnosis was clinical and biomarkers were not advised for routine use. In 2018, a research framework defined Alzheimer's biologically and required A+ and T+. In 2024, one abnormal Core 1 result, such as amyloid alone, is enough. ^254,255,347

Modelled

How long each phase lasts

Across 6 cohorts (3,268 people), someone with preclinical Alzheimer's at age 70 was estimated to spend about 10 years preclinical, 4 with MCI and 6 with dementia. Total duration ranged from 24 years starting at 60 to 15 years starting at 80. ⁵⁰¹

Exam hookAmyloid is necessary for the biological label but tracks symptoms poorly; neurodegeneration tracks symptom severity, and tau stage carries prognosis. In cognitively unimpaired people, against A−T−, the hazard ratio for progressing to dementia was 1.5 for stage A, 5.6 for medial temporal tau and 39.9 for neocortical tau. ^252,255