Lumbar Puncture and Cerebrospinal Fluid biomarkers

What a Lumbar Puncture is

A Lumbar Puncture is a procedure to obtain Cerebrospinal Fluid (CSF) from the lower back. Under local anaesthetic, a fine needle is inserted between two vertebrae in the lumbar spine into the fluid-filled space below the spinal cord. 10 to 15 mL of CSF is collected. The procedure takes around 30 minutes including preparation and recovery.

Lumbar Puncture is well-tolerated by most people. Modern atraumatic needles substantially reduce the risk of post-procedure headache.

What CSF biomarkers measure

The standard Alzheimer's CSF biomarker panel measures three proteins:

• Amyloid-beta 42 (Aβ42): reduced in Alzheimer's Disease, because amyloid is deposited in plaques in the brain rather than circulating in CSF;
• Total tau (T-tau): raised in Alzheimer's Disease, reflecting neuronal damage;
• Phosphorylated tau (P-tau): raised in Alzheimer's Disease, reflecting tau pathology specifically.

The Aβ42/Aβ40 ratio is increasingly used as a more reliable indicator than Aβ42 alone. A "positive" CSF profile (low amyloid, raised tau) supports Alzheimer's Pathology with high accuracy.

When CSF biomarkers are recommended

NICE NG97 recommendation 1.2.15 supports CSF biomarker measurement as an alternative to FDG-PET when Alzheimer's Disease is suspected but uncertain. Typical situations:

• Young-onset dementia where Alzheimer's Pathology needs confirmation;
• Atypical presentations (visual, language, executive) where pathology will inform management;
• Eligibility assessment for clinical trials of anti-amyloid therapies;
• Where future access to Lecanemab or Donanemab may be considered;
• Where the differential between Alzheimer's and Frontotemporal Dementia is unresolved.

What to expect on the day

You will be asked to lie on your side with knees drawn up, or sit forward over a table. Local anaesthetic is injected. A fine needle is then inserted under sterile conditions. The fluid collection takes 5 to 10 minutes. After the procedure, lying flat for an hour reduces the chance of headache.

You can usually go home the same day. Plan a relaxed day; avoid heavy lifting for 24 hours.

Risks and side effects

• Post-procedure headache: the commonest side effect, occurring in 1 to 10 per cent depending on the needle and technique. Modern atraumatic needles substantially reduce risk. Most headaches settle within a few days with rest, hydration and simple analgesia; rarely a "blood patch" procedure is needed.
• Back pain at the puncture site: mild and short-lived in most cases.
• Infection: very rare with modern sterile technique.
• Nerve injury or bleeding: very rare.

Contraindications include anticoagulant therapy (may need to be withheld), bleeding disorders, raised intracranial pressure (excluded by prior brain imaging) and local infection at the puncture site.

UK availability

NHS Lumbar Puncture is performed in memory clinics, neurology services and day-case units. Private CSF biomarker testing is available through specialist providers, typically costing £1,500 to £2,500 including procedure and laboratory analysis.

Future: blood-based biomarkers

Several blood-based tests for Alzheimer's Pathology (plasma p-tau, plasma Aβ42/Aβ40) are in active development. They are not yet in routine UK clinical use but may substantially reduce the need for Lumbar Puncture within the next few years.

Where to discuss

Lumbar Puncture for biomarker analysis is a specialist procedure. Discuss with your memory clinician or neurologist. The Dementia Service can arrange CSF biomarker analysis through partner providers where clinically indicated.