Start here: what Alzheimer disease is
Alzheimer disease is a neurodegenerative process characterized by progressive memory and functional decline, with shared pathology across a continuum rather than a single sudden transition [1]. The public-facing frame is useful: symptoms emerge from interacting biology—molecular stress, network failure, inflammation, and cumulative injury—not one isolated lesion [2].
Biologically, amyloid and tau pathways remain central for diagnosis and trial design, while synaptic and inflammatory pathways are now treated as co-equal contributors to symptom trajectories [3] [4] [5]. Clinically, diagnosis is increasingly a two-channel process: clinical syndrome plus biomarker confirmation in appropriate contexts [6] [7].
Pillar 1: measurements
Clinical phenotyping remains the front door. Standard cognition and function tests define syndrome severity and pace and remain necessary for treatment decisions and trial eligibility, even as biomarkers expanded the toolkit [6] [8].
Blood-based biomarkers are moving rapidly into routine care. Plasma p-tau and related plasma panels are now studied for earlier rule-in/rule-out workflows, especially when invasive cerebrospinal-fluid testing is not immediately available [7] [9] [10].
Amyloid- and tau-specific fluid/Imaging strategies remain complementary: amyloid PET and tau PET remain high-specificity anchors for some indications, while plasma markers improve accessibility and staging convenience in wider populations [7] [11] [9].
Longitudinal monitoring matters. Recent work increasingly uses trajectories (biomarker change over time, not only single thresholds) to support progression risk and treatment-response interpretation [12] [13] [14].
Pillar 2: medicines
The treatment ecosystem currently spans symptomatic support and disease-modifying attempts.
Symptomatic layer. Cholinergic strategies and cognitive-supportive medication continue to be used to maintain function when possible, especially early to moderate stages [11] [15].
Disease-modifying monoclonal antibodies are the front-line frontier in late-stage 2020s reports. The two that define the current landscape are lecanemab and donanemab, both of which have shown biomarker and clinical effects in selected early populations. Aducanumab was the first of the class to be authorized, but it is no longer the focus of the field or part of the treatment landscape; what carried forward from it are the implementation questions its evidence raised — how to select patients, how to monitor amyloid-related imaging abnormalities, and how much biomarker change translates into clinical benefit — which are now asked of its successors [16] [17] [18].
Adjunct pathways under study include microglial and inflammatory regulation, tau-targeting strategies, and vascular-metabolic interaction work in at-risk groups [5] [19] [20] [21].
Pillar 3: progress
The frontier is currently about selecting the right intervention for the right biology at the right stage:
- Biomarker-guided precision is moving from research language to protocols with explicit confidence thresholds and confirmatory pathways [22] [8].
- Anti-amyloid and anti-tau strategy design is becoming more about timing, safety, and durable benefit than whether the pathway can be engaged at all [23] [24].
- Non-amyloid biology is no longer “secondary”—microglial, synaptic, and inflammatory programs are now treated as parallel determinants of progression and response heterogeneity [21] [25] [20].
- Prevention and risk reduction remain important at the population level: vascular and lifestyle factors influence incidence and progression windows alongside molecular therapies [13].
No simple standalone closed-form model is included here
Alzheimer disease is a multi-scale, multi-pathway disorder. In this review we do not force a one-node model that would hide that complexity and distort therapeutic interpretation [26] [27]. We defer to network-level simulations handled at the trial/biomarker systems layer.
Dig deeper in lmmol
The molecular nodes this review turns on:
- Amyloid precursor protein (APP) — the parent protein from which amyloid-beta is cleaved.
- Presenilin-1 — the catalytic core of gamma-secretase, and the site of the classic autosomal-dominant mutations.
- Beta-secretase 1 (BACE1) — the other cleavage enzyme, and a therapeutic target in its own right.
- Acetylcholinesterase — the target of the symptomatic cholinergic drugs.
Related review in this series:
- Hypertension — vascular risk factors influence incidence and progression windows alongside molecular therapies.
For entities without a linked static page here, use the graph index, all diseases, or all proteins rather than guessing an entity URL.
Implementation & visualization hooks
lmvideo / diagramkit: render a progression schematic from symptom stage to biomarker layer to therapeutic action points, including uncertainty bands on diagnostic signals.