Center-Specific Center-Specific Neuropathology Procedures Neuropathology Procedures

SurveySurvey

Erin M. Pfeiffer10/12/2002

NACCNACCNational Alzheimer’s Coordinating Center

NACCNACC

Center-Specific Neuropathology Center-Specific Neuropathology SurveySurvey

Dr. Cochran, Dr. Dickson, Dr. Ghetti Special Thanks – Dr. Jim Leverenz

10-page detailed survey 90.6 % response rate (29/32 surveys) Complete answers & thoughtful

comments

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Survey FormSurvey Form

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Survey FormSurvey Form

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Survey FormSurvey Form

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Survey FormSurvey Form

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General Questions:General Questions:# NP-related data elements maintained in each # NP-related data elements maintained in each

Center’s DatabaseCenter’s Database

# Variables Stored Count Percent

1-25 5 18 %

26-50 2 7 %

51-75 5 18 %

76-100 5 18 %

> 100 11 39 %

Frequency Missing = 1

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General Questions (cont’d)General Questions (cont’d)

> 90% maintaining data on: AD pathological dx Plaques/tangles PD pathological dx Lewy bodies Infarcts

~ 46% maintain genetic data

~ 62% collect circumstance of death (Including Centers who collect for some/not all subjects)

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Specimen and Tissue Specimen and Tissue Preparation:Preparation:

Postmortem IntervalPostmortem Interval

0

2

4

6

8

10

12

14

16

0-4 hrs

5-8 hrs

8-12 hrs

Postmortem Interval (hrs)

# o

f C

en

ters

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Specimen and Tissue Specimen and Tissue Preparation:Preparation:

Specimens Collected from AutopsySpecimens Collected from Autopsy

Percent of Centers Collecting Samples

Specimen Type

Fixed Paraffin Frozen None

Hippocampus 86 % 100 % 93 % --

Temporal Cortex

86 % 100 % 90 % 3 %

Pituitary Gland 12 % 28 % 14 % 52 %

PNT* 7 % 7 % 3 % 93 %* PNT = Peripheral Nervous Tissue

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Specimen and Tissue Specimen and Tissue Preparation:Preparation:CryoprotectionCryoprotection

40% store fixed tissue in cryoprotective solution

Average time tissue fixed prior to transfer to cryoprotective solution = 2 days

Cryoprotective solutions include:– 16% sucrose– 20% glycerol, 2% DMSO– Isopentane Liquid Nitrogen– Sucrose/ethylene glycol in phosphate buffer

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Specimen and Tissue Specimen and Tissue Preparation:Preparation:

Biological Specimen BankingBiological Specimen Banking

Biological Specimen

Count Percent

DNA 17 63 %

Serum 13 48 %

Lymphocytes: Buffy Coat

8 30 %

Lymphocytes:Lymphoblastoid ICL*

1 4 %

Antemortem CSF 5 19 %* ICL = Immortalized Cell Lines

Frequency Missing = 2

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Stains for identifying beta-amyloid pathology

– 69 % Silver Stain (e.g. Bielschowsky, Bodian, Campbell-Switzer, Microwave King, Gallyas)

– 35 % Thioflavin-S

– 24 % Congo Red

– 72 % Aß immunostain (e.g. GFAP, Novocastra, DAKO monoclonal mouse)

Histopathology:Histopathology:StainsStains

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Stains for identifying neurofibrillary pathology

– 76 % Silver Stain (e.g. Bielschowsky, Modified-Biel,

Bodian, Microwave King, Gallyas)

– 36 % Thioflavin-S

– 83 % Tau immunostain (e.g. AT8, PHF-1, ALZ-50, Tau-2)

Histopathology:Histopathology:StainsStains

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Neuropathology:Neuropathology:CriteriaCriteria

AD Pathology Count Percent

NIA/Reagan Institute 25 86 %

CERAD 22 76 %

ADRDA/Khachaturian

6 21 %

Tierney -- --

Other * 5 17 %

* Washington U modified Koch (1985), In house semi-quantitative methods, etc

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Neuropathology:Neuropathology:CriteriaCriteria

FTD Pathology Count Percent

Lund and Manchester* 9 32 %

Work Group on FTD & PiD** 19 68 %

Other 4 14 %

* Lund and Manchester Groups. Clinical and neuropathological criteria for frontotemporal dementia. J of Neurology, Neurosurgery, and Neuropsychiatry 1994:416-18

**McKhann GM et al. Clinical and Pathological Diagnosis of Frontotemporal Dementia: report of the work group on frontotemporal dementia and Pick’s disease. Arch of Neurol 2001:1803-09

Frequency Missing = 1

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Percentage of Centers that perform:– Immunoassays = 40%– In situ hybridization = 14%– Image analysis = 36%– Stereology = 25%– Microarray analysis = 32%

Additional Procedures:Additional Procedures:Performed on NP core tissuePerformed on NP core tissue

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Summary / Plans for NP Survey DataSummary / Plans for NP Survey Data Detailed summary of NP procedures & specific specimens available at each ADC

Dataset created - After NYC, contact a few ADCs for brief clarifications

Survey results will be available via NACC’s website Data will be integrated into overall database (i.e. linked to MDS, Neuropathology data, other Centers data)

Thanks again!

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