Trials and tribulations of using beta-amyloid precursor protein immunohistochemistry to evaluate traumatic brain injury in adults.
Axonal pathology is increasingly identified by beta-amyloid precursor protein (betaAPP) immunohistochemistry in the brains of patients who may or may not have a history of trauma. The presence of betaAPP-IR(+) has been variously interpreted as either that diffuse traumatic axonal injury (TAI) is indeed a universal finding in cases of fatal traumatic brain injury (TBI) or there are other causes of betaAPP-IR(+) axons which under certain circumstances may be sufficient to mimic TBI and therefore make the medico-legal interpretation of certain cases very difficult. To address some of the uncertainties we have undertaken a detailed analysis of the amount and distribution of betaAPP immunohistochemistry in 63 cases of fatal TBI, 17 cases of patients dying after cardiac arrest, 12 cases dying in association with status epilepticus, 3 cases of carbon monoxide (CO) poisoning, 13 cases of hypoglycaemia and in 60 controls. Three patterns of betaAPP-IR(+) were identified. First, diffuse multi-focal, second, corresponding to the outline of an infarct or haematoma, and thirdly a mixture of the two. The first pattern was seen in cases of the lesser grades of TAI, CO poisoning, and hypoglycaemia, the second pattern in cases in which there was evidence of raised intracranial pressure and the third in cases of severe TAI. It is concluded that the proper interpretation of cases requires the examination of a sufficient number of blocks ( [Formula: see text] ), processing using standardised protocols including betaAPP immunohistochemistry and in some cases the mapping of any IR(+) on anatomical line diagrams. betaAPP carried out on a small number of randomly taken blocks is likely to lead to misinterpretation of the clinico-pathological correlations and possibly to a miscarriage of justice.
Graham
D I
DI
Academic Unit of Neuropathology, Division of Clinical Neuroscience, Institute of Neurological Sciences, Southern General Hospital NHS Trust, Glasgow, Scotland, UK. d.graham@clinmed.gla.ac.uk <d.graham@clinmed.gla.ac.uk>
Smith
C
C
Reichard
R
R
Leclercq
P D
PD
Gentleman
S M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002249:Carbon Monoxide Poisoning / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D049429:Forensic Pathology; D006323:Heart Arrest / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007223:Infant; D019586:Intracranial Hypertension / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013226:Status Epilepticus / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D016229:Amyloid beta-Peptides