UK Parkinson’s Disease Society Tissue Bank at Imperial College London

Email: pdbank@imperial.ac.uk

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Support Workers Talk
Why donate your brain to the Parkinson's Disease Society (PDS) Tissue Bank?

Introduction
  • Background of the Tissue Bank
  • Aims and Objectives of the Tissue Bank
  • Reasons why it is important to donate?
  • Who can donate?
  • What is involved in registering to be a donor?
  • What is involved in donation procedure?
  • How will the tissue be used?
  • PD research
  • Donor statistics to date and clinical information
  • What happens if you want to donate? - Contact details

Background of the Tissue Bank

Expert review committee of the Parkinson's Disease Society (PDS) moved its Brain Tissue Research Centre from the Institute of Neurology to Imperial College in January 2002.

  • Bring together scientists researching PD, neurologists, neuro-pathologists
  • Imperial college already housed tissue collections including the Multiple Sclerosis Tissue Bank

Letter sent from the PDS to all existing tissue donors explaining the changes.

New set of consent forms

Aim of the Tissue Bank

Develop a framework allowing successful interactions between:

Bringing together researchers and neuropathologists with people affected by PD.

Objectives of the Tissue Bank

To obtain and distribute High Quality human brain tissue, for research into PD and related disorders both in the UK and worldwide.

  • Recruitment into donor scheme
  • Collection of patient data, family histories, epidemiological details
  • Collection, processing and storage of human tissue
  • Distribution of tissue to scientists
  • Raise public awareness, links with international PD research and interest groups
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Why do we need a PD Tissue Bank?

HUMAN Brain Tissue is VITALLY IMPORTANT for ongoing progress into the understanding and treatment of neurological disorders such as Parkinson's Disease.

  • Why human?
    • Animals don't get PD, hence donated tissue is essential for examining the mechanisms of cell death, pathological changes etc.
    • Complement some animal work and tissue culture studies, and provide confirmation of these studies
  • Past research:
    • Drug development - L-DOPA
    • Some understanding of mechanisms of cell death

Who can donate tissue?

Anyone!

  • Parkinson's Disease
  • 'Parkinson's plus' movement disorders:
    • Multiple System Atrophy (MSA)
    • Progressive Supranuclear Palsy (PSP)
  • Controls – very important

With Human tissue there is always a great demand!

What is involved in registering to be a donor?

  • follow government guidelines for tissue donation
  • information pack
  • donor consent
  • next of kin consent form
  • GP copy of forms
  • Historical data on lifestyle and family

Information stored about our donors

  • Request for information
    • name and address
  • Donor information obtained:
    • donor consent form
    • next of kin consent form
    • historical data on lifestyle and family
  • After death
    • clinical/medical notes

Donor Cards

One of our donor cards.

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What is involved in the donation procedure?

Rapid collection of tissue is important (Aim - 24 hours)

  1. Death of registered donor
  2. Next of kin calls PDS Tissue Bank 24 hour emergency telephone number
  3. PDS Tissue bank immediately calls for further details
  4. Deceased transported to nearby hospital for tissue removal
  5. Body returned to funeral directors
  6. Tissue collected and stored at Charing Cross Hospital

What happens when a donor dies?
  • 24 hour on call rota
  • Make arrangements –
    • Post Mortem Delay?
    • Fixed or Fresh tissue? (Majority Fresh)
  • 2 ways of processing

What will happen to my brain once donated?

Two methods of processing donated tissue.

What will happen to my brain once donated?

The brain is cut into two halves, one of which is fixed. The other half is cut into thick sections and rapidly frozen.

For the fixed half, tissue blocks from various brain regions are cut. Tissue sections from such blocks are subjected to a variety of histological stains. A neuropathologist examines the sections to confirm that the donor had a specific neurological disease or was free from any neurological disorder.

Once the neuropathological diagnosis has been confirmed, the frozen tissue slices dissected and utilised for the various research projects.

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What will happen to my brain once donated?

When the tissue is taken fresh, half it is sliced, and the slices cut into blocks, which are then snap-frozen. The slices are photographed before and after blocking.

What will happen to my brain once donated?

When the tissue is taken fresh, half it is sliced, and the slices cut into blocks, which are then snap-frozen. The slices are photographed before and after blocking.

What will happen to my brain once donated?

When the tissue is taken fresh, half it is sliced, and the slices cut into blocks, which are then snap-frozen. The slices are photographed before and after blocking.

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What will happen to my brain once donated?

After 4 to 6 weeks in fixative, the fixed tissue is dissected. As with the

What will happen to my brain once donated?

After 4 to 6 weeks in fixative, the fixed tissue is dissected. As with the

"Looking at post-mortem brain tissue is like looking at the scene of a crime. You are trying to gather evidence to find out what has happened!"

Some of the tissue-bank board members seated around a multi-headed microscope.

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Tour of Tissue Bank

Laboratory for brain dissection The solid bench shown in this picture has since been replaced by a downflow bench to draw and toxic vapours away from the dissectors. The laboratory is set up for a fresh dissection, with brain knife, scalpel, scissor, ruler, slicing guide and blocking grid laid out upon one cutting board (used to slice and photograph the brain). A second cutting board holds weighing scales, cryotubes, pipette, brain knife, scalpel and support board, and is used for weighing the brain, taking the pH of any cerebrospinal fluid and pipetting 1ml aliquots into cryotubes and cutting brain slices into blocks. A large polystyrene box is filled with dry ice, which is used to cool a tray of isopentane. This is used to snap-freeze tissue blocks.
The tissue bank brain dissection room, showing the central downflow bench surrounded by dissectors wearing disposable gowns and gloves. For fresh dissections, masks with face guards are also worn. A fixed brain currently sits upon the cutting board on the downflow bench. A camera sits above the cutting board and is operated using a computer. Dissection of a fixed hemi-brain. The hemi-brain is sliced coronally and the slices laid out on the cutting board for examination by the neuropathologist. Once he has recorded his observations, he takes the blocks for neuropathological diagnosis, which are placed in processing cassettes and left in formalin for a week. Once the neuropathologist has finished, technicians from the tissue bank photograph each slice on both sides and cut them into blocks, as with a fresh dissection. After blocking, the slices are re-photographed. The blocks go into sucrose in the fridge for a week and are then frozen in cooled iso-pentane.

Tour of Tissue Bank

Laboratory for brain dissection – photographing of tissue

The digital camera used to photograph tissue during the dissections, together with the computer used to operate it. A whole, unfixed brain, looking from the top down.   A whole, unfixed brain, looking from the right-hand side.

The two hemispheres of an unfixed brain, looking from the top down, after they have been separated.   The inner face of the right hemisphere of an unfixed brain.

Tour of Tissue Bank

Laboratory for brain dissection – photographing of tissue

The digital camera used to photograph tissue during the dissections, together with the computer used to operate it. Below:
Substantia nigra from a normal (control) brain – darkened/pigmented area

A control brain, showing the substantia nigra.   The brainstem and cerebellum from a control brain, showing the substantia nigra.

Below:
Substantia nigra from PD brain – pale/depigmented area

A PD brain, showing the substantia nigra.   The brainstem and cerebellum from a PD brain, showing the substantia nigra.

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Tour of Tissue Bank

Laboratory for brain dissection – photographing of tissue

The digital camera used to photograph tissue during the dissections, together with the computer used to operate it. A slice of an unfixed hemi-brain.   The other side of the same brain slice.

A slice of an unfixed hemi-brain, cut into blocks along the grid-lines.

Tour of Tissue Bank

Laboratory for brain dissection – Freezing of blocks

A thick layer of dry ice is laid on the bottom of a large polystyrene box. A metal tray with a grid-insert of 8 x 8 squares is placed on top of this and dry ice packed around the edges to chill the whole thing. The tray is filled with isopentane. Tissue blocks to be frozen are placed in the wells of the tray. When they are frozen all the way through, they are placed in 8-well plates. Each well is labelled with the slice number and grid reference of the block. Filled plates are put in freezer bags (two to a bag), which are stored in a -85oC freezer. An 8-well plate filled with frozen blocks of tissue. Each well is labelled with the slice number and grid reference of the block.

One of the -85oC freezers used for the long-term storage of tissue.

A freezer room shared with the Multiple Sclerosis Tissue Bank, also based at Imperial College London.

Tour of Tissue Bank

Histology Laboratory

A tissue processing machine. The blocks for neuropathological analysis are placed in the chamber of the processor, which immerses them in a series of liquids and then infiltrates them with wax, ready for embedding. The embedding machine. Once the tissue blocks have been infiltrated with wax, they are placed in embedding troughs which are filled with molten wax and then allowed to set. Embedding tissue blocks in wax preserves the morphology of the tissue and makes the anatomy easier to analyse.

The microtome is used to cut very thin sections from the wax-embedded tissue blocks. These can then be stained with a variety of different dyes and/or antibodies.

Tour of Tissue Bank

Histology Laboratory

Two of the tissue bank techicians look down the microscope at a stained tissue section. A section of substantia nigra from a Parkinsonian brain, stained with haematoxylin and eosin. Lewy bodies are indicated by arrows.   A section of substantia nigra from a Parkinsonian brain, stained with haematoxylin and eosin. Lewy bodies are indicated by arrows.

A histological section of Parkinsonian Substantia nigra depicting a dopaminergic neurones containing Lewy Bodies.

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Tour of Tissue Bank

Histology Laboratory

Top right: Control tissue

Two of the tissue bank techicians look down the microscope at a stained tissue section.

Bottom right: PD tissue

A section of substantia nigra from a control brain, stained with haematoxylin and eosin.   A section of substantia nigra from a control brain, stained for alpha-synuclein. The brown deposits are neuromelanin - the section is negative for alpha-synuclein.

A section of substantia nigra from a Parkinsonian brain, stained with haematoxylin and eosin.   A section of substantia nigra from a Parkinsonian brain, stained for alpha-synuclein. The brown deposits are all positive staining.

Progress of the new Tissue Bank

  • Number of donors on the database and information set out to possible donors – going well but need to increase
  • Designed a new information sheet
  • New donor cards sent out to registered donors
  • Databases
  • Laboratory up and running
  • Website – www.parkinsonstissuebank.org.uk
  • New Logo

Statistics of the PDS Tissue Bank donors

  • Number of enquiries/ request for information
  • Number of donors registering
  • Donor Distribution

Donor Statistics

  Pre-July To Date
Requests for information
(Packs sent) 		272 1555

Bar chart showing the number of information packs sent out between July 2002 and July 2006.

Donor Statistics

Bar chart showing prospective donor registration each month between July 2002 and July 2006.

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Donor Statistics

Bar chart showing cumulative prospective donor registration between July 2002 and July 2006.

  Pre-July Total To Date On system
(Current)
Total number of donors registered 139 954(366) 774(353)

Donor Statistics

Pie chart showing the percentage of PD and control cases procured.

Donor Statistics

Bar chart comparing the number of packs sent our with the number of new registrations received, for each month between July 2002 and July 2006.

Donor Statistics

  Number of donors Number of Males Number of Females Number of Males with PD Number of Females with PD Number of Males without PD Number of Females without PD
Registered/ Prospective 774 321 453 220 201 101 252
Cases 151(+29) 102(+13) 49(+16) 97(+13) 45(+12) 5 4(+4)
Total 954 436 518 330 258 106 260

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Donor Statistics - Distribution of Donors

Bar chart showing geographical distribution of prospective donors.

Donor Statistics - Age Distribution of Donors

Bar chart showing the age distribution of prospective donors.

Procurement of Tissue

Bar chart showing the number of cases procured each month between July 2002 and July 2006.

Procurement of Tissue

Pie chart showing the proportion of PD, control and disease control cases.

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Clinical Review

Diagnoses (PD1-46, 48, 53-56)

Pie chart showing the proportion of the different diagnoses for cases up to June 2004.

Clinical Review

Donors

  • Mean Age at Onset: 65 (32-85)
  • Mean Age at Death: 77 (42-93)
  • Mean Duration of Illness: 12 (2-43)
  • Female: Male (28%: 72%)

Clinical Review

Bar chart showing the age at onset for the cases.

Clinical Review

Bar chart showing the age at death for the cases.

Clinical Review

Bar chart showing the disease duration for the cases.

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Clinical Review

Pie chart showing mode of presentation for the cases.

Clinical Review

History I

  • Non-(never/reformed) smokers 46/51 (90%) (For 2 donors status unknown)
  • Active smokers 3/51 (6%) (All with atypical features & ?Cerebrovascular Parkinsonism)
  • Positive Family History 7/51 (14%)

Clinical Review

History II

  • Neuroleptic exposure 6/51 (12%)
  • PD8: Methanol/Formaldehyde exposure
  • PD15: Crop Spraying exposure
  • Dyskinesia 22/51 (43%)

Clinical Review

Bar chart showing the percentage of cases exhibiting different neuropsychiatric symptoms.

Clinical Review

Bar chart showing the percentage of cases exhibiting different autonomic symptoms.

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How will the tissue be used?

  • Requests for tissue from recognised Institutions both in the UK and around the world.
  • The project is reviewed by an independent scientific panel, to check whether the project is scientifically sound and will benefit medical research.
  • Written report on the research carried out by the research team.
  • Acknowledgement of the Tissue Bank and PDS in any scientific publication where donated tissue has been used.

What are the aims for PD Research?

  • Understand how and why cell death occurs in PD
  • Develop better treatments in PD and related diseases
  • Predict and identify possible susceptibility to PD
  • Disease prevention

PD Research being carried out at Imperial

Dr David Dexter - Mechanisms of Neuronal death

  • Accumulation of Fe in the PD Substantia nigra – Stimulation of free radicals.
  • Increased free radical damage to lipids and other cellular components.
  • Deficiency of the bodies defence systems against free radicals – antioxidants.
  • Studies with Vitamin E and C
  • Are they the best anti oxidants to use? – Flavonoids
  • Flavonoids - Found in many fruits, vegetables, seeds, grain, tea & wine. Also anti-inflammatory

Dr David Dexter - What has sex got to do with Parkinson’s Disease

  • Epidemiology studies reveal that women are less likely to develop PD!
  • Pre-menopausal women with PD experience clinical fluctuation to drugs during the estrous cycle.
  • Removal of hormone replacement therapy in post-menopausal women worsens PD!
  • Is estrogen neuroprotectory?

Professor Manuel Graeber – Gene Expression analysis

  • 33,000 genes to look at!
  • Concentrate on the genes responsible for the mechanisms of cell death that we have identified so far e.g. oxidative stress.
  • Once we have identified genes that are either up or down regulated we will look at their expression at the cellular level i.e. does it occur in neurones, glia etc

Microarray Technology

Diagram illustrating microarray technology.

UV Laser Capture Microdissection

Isolation of specific cells using UV laser-capture microscopy.

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Tissue Bank – Publicity (1)

  • Branch Talks (some with press coverage) –
    Bath, Worthing, Aberystwyth, Barnet, Horsham, Sevenoaks, North Herts/Stevenage, Croydon, Northampton, Cheltenham, Doncaster, Brentwood, Lincoln, Rugby, Christchurch, Leicester, Poole, Beccles, Byfleet, Malmesbury, Bradford, Dumfries, Oldham, Halifax, Worcester, Newbury, Longeaton, Bracknell, Portsmouth, Ashford, Stevenage (YAPP&Rs), NW Branches, South Anglia, Plymouth, Southampton, Dundee, Greenwich, Peterborough, Barking, Harlow, Hitchin, Lewisham, Oxford, Hampshire (YAPP&Rs), Basingstoke, Southend, Haltwhistle, Penrith, Welwyn and Hatfield, Guildford Dartford, Amersham, Liverpool, Sutton, Kingston and Epsom, Hillingdon, Lincoln, York, Hull, Derby, Farnborough, Minehead, NW Somerset, Southport, Maidenhead, Barnsley, West Midlands, Stockport, Sandwell, Canterbury, Eastbourne, Cirencester, Bristol, Harrogate, Beccles, Cardiff, Newport, Aberdeen, Chichester, Reigate, Leamington, Bridport, West Herts.

  • PDS AGM 2001, 2002, 2004 and 2005. YAPP&R’s AGM 2005.

  • Scottish Branches meeting in Stirling.

  • Northern Ireland Branches Meeting in Cookstown.

  • BA Festival of Science, Dublin September 2005

Tissue Bank – Publicity (2)

  • Meeting of PD nurse specialists in Nottingham. Community and support workers – Reading 2004, Kensington 2004

  • Donate for the future article – "Parkinson" Magazine.

  • SPRING conference – 11th March 2003

  • Brain Awareness Week – 10th-14th March 2003

  • PD nurse visit arranged by GSK – 25th March and 4th Nov 2003, 9th Jan and 13th Feb 2004, 18th November 2005

  • Tissue Bank open day – 28th March 2003, 16th April 2004, 11th April 2005

  • Article for Working With Older People – June 2003

  • Articles in YapMag – August 2003, Winter 2003

  • Articles in Branch literature – Worcester, Lewisham, North Herts (YAPP&Rs), Mid Somerset, North London, Guildford, Hillingdon, Taunton, Dorset (YAPP&RS)

  • First Newsletter Out September 2003, Second April 2004, Third September 2004, Fourth April 2005, Fifth September 2005

  • Sixth newsletter Out Now!!!

Donate for the Future

The UK PDS Tissue Bank logo.

"DONATION OF YOUR BRAIN IS ONE OF THE MOST IMPORTANT LEGACIES YOU CAN MAKE TO THE ADVANCEMENT OF RESEARCH INTO PARKINSON’S DISEASE AND OTHER NEUROLOGICAL DISORDERS!"

Contact Details

UK Parkinson's Disease Society Tissue Bank at Imperial College

Division of Neuroscience & Psychological Medicine
Imperial College of Science Technology & Medicine
Faculty of Medicine
Charing Cross Campus
Fulham Palace Road
London
W6 8RF

Tel: (Int +44-20) 020-8383-4917
Fax: (Int +44-20) 020-8383-4918

Email: pdbank@imperial.ac.uk

Website: www.parkinsonstissuebank.org.uk/

Contact us and we will send you an information pack

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