Alzheimer's antibodies: lecanemab and donanemab guide

What are amyloid beta plaques, and why are they a treatment target?

Alzheimer's disease is defined neuropathologically by extracellular beta-amyloid deposits forming neuritic plaques and by intracellular accumulation of hyperphosphorylated tau forming neurofibrillary tangles^[1]. The amyloid hypothesis holds that an imbalance between production and clearance of amyloid beta 42 and related peptides is a very early, often initiating factor in the disease^[2].

That hypothesis rests on genetic evidence. All dominant mutations causing early-onset Alzheimer's disease occur either in the amyloid precursor protein (APP) or in presenilin, the catalytic site of the gamma-secretase that generates amyloid beta. Low amyloid beta 42 in cerebrospinal fluid and a positive amyloid PET scan precede other manifestations of Alzheimer's disease by many years^[2]. The risk of Alzheimer's disease is 60–80% dependent on heritable factors, and the APOE alleles show the strongest association with the disease among more than 40 identified risk loci^[3].

Two consequences follow for patients. First, a treatment aimed at amyloid beta is most plausibly tested in people at an early stage. At this stage, plaques are present but dementia is still mild. Second, confirming that plaques are actually present requires a biomarker test. This may be amyloid PET imaging or a plasma or cerebrospinal fluid assay, not symptoms alone. The biomarker requirement also makes these therapies logistically different from most chronic disease medicines. The biological target has to be demonstrated before the first infusion. That demonstration relies on imaging or fluid assays rather than on the clinical picture^[3].

How do lecanemab and donanemab work?

Both medicines are monoclonal antibodies – a type of protein that attaches to a specific target. Lecanemab attaches to amyloid beta and, by binding it, reduces amyloid plaques in the brain^[4]. Donanemab also attaches to amyloid beta, and by doing so activates microglial cells, the brain's immune cells, to clear the amyloid deposits, which reduces plaques^[5].

The distinction matters when you read about the medicines. Lecanemab is described as binding amyloid beta and lowering plaque load; donanemab's description adds an immune-mediated clearance step through microglia^[4][5]. Because both antibodies act on the same deposited protein, they sit within the same mechanistic family – the anti-amyloid beta approach that the review literature identifies among the pharmacological strategies reaching advanced stages of clinical trials^[3].

Who are these medicines authorised for in the European Union?

Both medicines are authorised in the European Union for adults with mild cognitive impairment and mild dementia due to Alzheimer's disease – that is, early Alzheimer's disease^[4][5]. Eligibility is narrower than the diagnosis alone: the person must have only one or no copy of the ApoE4 gene and must have amyloid beta plaques in the brain^[4][5].

The ApoE4 restriction is not administrative. The benefits of lecanemab were assessed in the subgroup of patients with only one or no copy of ApoE4, who are less likely to experience ARIA than people with two copies^[4]. For donanemab, a test to determine ApoE4 gene status is part of the treatment pathway^[5]. In practice, then, a conversation about these medicines begins with two laboratory or imaging results – ApoE4 genotype and amyloid status – before it reaches the question of infusions at all^[4][5].

How are the medicines given and monitored?

Both are prescription-only infusions (drips) into a vein, but on different schedules and with different monitoring rules.

Feature	Lecanemab (Leqembi)	Donanemab (Kisunla)
Route	Intravenous infusion[4]	Intravenous infusion[5]
Schedule	Once every two weeks[4]	Once every four weeks[5]
Who starts treatment	A doctor experienced in diagnosing and treating Alzheimer's disease, with timely access to MRI[4]	A doctor experienced in diagnosing and treating Alzheimer's disease[5]
Pre-treatment MRI	Before starting treatment[4]	In the 6 months before starting treatment[5]
Further MRI scans	Before the 5th, 7th and 14th dose; additional scans if symptoms suggest ARIA[4]	Before the 2nd, 3rd, 4th and 7th dose[5]
Review of benefit	Cognitive function and symptoms assessed about every 6 months; treatment stopped on progression to moderate Alzheimer's disease, and the doctor considers stopping if there is no benefit[4]	Treatment should not exceed 18 months[5]
Key restriction	–	Must not be used in people with inadequately controlled bleeding disorders or in those receiving anticoagulant treatment[5]

For lecanemab, the infusion should be given by qualified healthcare professionals trained to monitor for, recognise and manage infusion-related reactions, and the supervising doctor must have timely access to MRI^[4]. For donanemab, treatment should be given under supervision of a team trained to detect, monitor and manage ARIA and infusion-related reactions^[5]. The practical consequence is that the dosing interval shapes daily life differently for each product: a fortnightly visit for lecanemab versus a four-weekly visit for donanemab, each still bound to its own imaging timetable^[4][5].

What did the main clinical studies measure, and what were the results?

The two programmes used different primary endpoints, so the numbers are not directly interchangeable.

Lecanemab: CDR-SB after 18 months

The main study involved 1,795 people with early Alzheimer's disease who had amyloid beta plaques in the brain and received either lecanemab or placebo. The main measure of effectiveness was change in symptoms after 18 months on the CDR-SB dementia rating scale, which ranges from 0 to 18, with higher scores indicating greater impairment. In the subgroup of 1,521 patients with only one or no copy of ApoE4, the increase in CDR-SB score after 18 months was 1.22 with lecanemab versus 1.76 with placebo. Other key measures were in line with the CDR-SB results^[4].

Donanemab: iADRs after 76 weeks

The donanemab study involved 1,736 patients with early Alzheimer's disease and amyloid beta plaques who received donanemab or placebo. The main measure was change in symptoms after 76 weeks on the integrated Alzheimer's disease rating scale (iADRs), which measures cognitive and functional ability and ranges from 0 to 144, with lower scores indicating worse ability. After 18 months of treatment, the iADRs score worsened by 11 points with donanemab and by 13 points with placebo^[5].

Both results are average changes in a group. They were measured at a fixed time point. People were selected for early disease. For the lecanemab analysis, they were also selected for ApoE4 status. These results describe a slower worsening on a rating scale. They are not a measure of how an individual person will function^[4][5]. This framing reflects the wider history of the field. Many phase 3 trials in Alzheimer's disease have failed to demonstrate benefit. A positive result is therefore read together with its endpoint, population and duration rather than in isolation^[1].

What is ARIA, and why do you need repeated MRI scans?

ARIA – amyloid related imaging abnormalities – is a side effect seen on brain imaging that involves swelling and potential bleeding in the brain^[4][5]. It is the reason both treatment pathways include scheduled MRI scans before specified doses^[4][5].

For donanemab, the most common side effects, which may affect more than 1 in 10 people, include ARIA-H (haemorrhage), involving small bleeds in the brain, ARIA-E (oedema), involving accumulation of fluid in the brain, and headache. The most frequent serious side effects were ARIA-H, ARIA-E and allergic reactions, including infusion-related reactions. Infusion-related reactions may include redness, chills, feeling sick, vomiting, sweating, headache, chest tightness, shortness of breath and changes in blood pressure^[5].

If you develop symptoms that suggest ARIA at any time during lecanemab treatment, additional MRI scans may be carried out, and the doctor may interrupt treatment temporarily or stop it altogether based on the MRI results. The pre-treatment MRI serves a second purpose beyond safety surveillance: it establishes a baseline against which later scans can be compared when interpreting whether imaging changes are new^[4][5].

What happens step by step when you take part in a clinical trial?

A trial of this type tests a hypothesis about mechanism in people, and the design follows from that hypothesis. The steps below describe what a participant encounters.

• Defining the target and the hypothesis. Amyloid beta dyshomeostasis is the most extensively validated therapeutic target in Alzheimer's disease, supported by genetic, biomarker and pathological evidence^[2]. Anti-amyloid beta strategies are among the pharmacological approaches that reached advanced stages of clinical trials^[3].
• Selecting participants by biology, not only by symptoms. Participants must have amyloid beta plaques confirmed, and ApoE4 status determines eligibility for these medicines^[4][5]. Novel biomarkers include PET scans and plasma assays for amyloid beta and phosphorylated tau^[3].
• Comparing against placebo. In both main studies, participants received either the antibody or a placebo (a dummy treatment), and change in symptoms was compared between groups at a pre-specified time point^[4][5].
• Choosing a scale that captures daily life. CDR-SB includes questions on how much daily life has been affected by cognitive impairment; iADRs measures cognitive and functional ability, that is, the ability to carry out daily tasks^[4][5].
• Pre-specified safety monitoring. MRI at fixed dose points and symptom-triggered MRI are built into the protocol for ARIA detection^[4][5].
• Regulatory assessment of the whole package. The European Medicines Agency assessed the study data, and the European Commission authorised both medicines for use in the European Union^[4][5].

The wider record is relevant to how you read news about trials. Many phase 3 trials in Alzheimer's disease have failed to demonstrate benefit, which is why a positive result is reported together with its endpoint, population and duration^[1].

Where can you look for a study?

Trials are listed in public registries where you can check that a study exists, what it tests and whether it is recruiting. Registries used for this purpose include ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Trials recruiting in Europe can also be searched on clinicaltrials.eu. Registry records are also where the mechanistic rationale of a study is stated in the researchers' own words, which lets you compare a recruiting trial against the strategies described in the review literature^[3].

Before contacting a site, note the eligibility criteria that appear in the registry record for these programmes: confirmed amyloid beta plaques and ApoE4 status^[4][5]. A registry entry is not a guarantee of access; the study team confirms eligibility^[4][5].

What comes after antibodies, and what is still experimental?

Antibody clearance of plaques is one strategy among several. Anti-amyloid beta, anti-tau and anti-inflammatory strategies are all in advanced stages of clinical trials. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology but can still contribute to a positive outcome in people with the disease^[3].

A different modality is targeted protein degradation. Proteolysis-targeting chimeric (PROTAC) molecules harness the ubiquitin-proteasome system to degrade a target protein. After two decades, the field has moved from academia to industry, with numerous companies disclosing preclinical and early clinical programmes. Clinical proof of concept for PROTAC molecules was provided in 2020 against two well-established cancer targets, and the field is now pursuing targets previously considered undruggable. This is early-stage work: the reported proof of concept is in oncology, not in Alzheimer's or Parkinson's disease^[6].

For Parkinson's disease, the supplied materials do not describe antibody or degradation-based treatments, so no clinical claims are made here. For any medicine you are offered, the product information and the treating doctor are the reference points for use and monitoring^[4][5].

When should you contact your doctor or care team?

Contact the team supervising treatment if, at any point during therapy, you notice symptoms that could suggest ARIA – the treating doctor may then arrange additional MRI scans and decide whether to interrupt or stop treatment^[4]. Report symptoms during or shortly after an infusion, such as redness, chills, feeling sick, vomiting, sweating, headache, chest tightness, shortness of breath or changes in blood pressure, as these are recognised infusion-related reactions^[5].

Tell the treating team about any bleeding disorder or anticoagulant treatment before starting donanemab. The medicine must not be used in people with inadequately controlled bleeding disorders or in those receiving anticoagulant treatment^[5]. Attend the scheduled MRI scans. For lecanemab these fall before treatment and before the 5th, 7th and 14th dose. For donanemab they fall before the 2nd, 3rd, 4th and 7th dose^[4][5]. Ask about the review schedule. Lecanemab treatment is stopped on progression to moderate Alzheimer's disease. The doctor considers stopping it if there is no benefit. Donanemab treatment should not exceed 18 months^[4][5]. It also helps to ask, at the start, who is responsible for each element of the pathway – prescribing, infusion supervision and imaging. The product information assigns distinct roles to the treating doctor and the infusion team^[4][5].

Summary

Three practical points follow from the documents above. First, check the eligibility conditions before discussing these medicines. Confirmed amyloid beta plaques and ApoE4 status are required^[4][5]. Second, plan around the MRI schedule from the first infusion, not after a symptom appears^[4][5]. Third, read study results with their endpoint and time frame attached. The figures 1.22 versus 1.76 on CDR-SB in 1,521 patients over 18 months are group averages on a named scale. The figures 11 versus 13 points on iADRs in 1,736 patients over 18 months are also group averages on a named scale^[4][5].

For experimental options, ask specifically which phase a programme is in and in which disease it was tested; the PROTAC proof of concept reported in 2020 was in oncology^[6].

This article is for information only and does not replace advice from your doctor, pharmacist or care team.

1. [1] Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (accessed 2 June 2026) — https://europepmc.org/article/MED/31564456
2. [2] The amyloid hypothesis of Alzheimer's disease at 25 years (accessed 2 June 2026) — https://europepmc.org/article/MED/27025652
3. [3] Alzheimer's disease (accessed 2 June 2026) — https://europepmc.org/article/MED/33667416
4. [4] Leqembi | European Medicines Agency (EMA) (accessed 2 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/leqembi
5. [5] Kisunla | European Medicines Agency (EMA) (accessed 2 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/kisunla
6. [6] PROTAC targeted protein degraders: the past is prologue (accessed 2 June 2026) — https://europepmc.org/article/MED/35042991
7. [7] Page or document not found | European Medicines Agency (EMA) — European Medicines Agency (EMA) (accessed 20.10.2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/produodopa