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We studied immunohistochemically the expression of β-amyloid precursor protein (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz-type protease inhibitor (KPI) domain, residues 1–28 of β protein (Affi28), and the car☐yl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and glial cells, and that for Affi28 in glial cells in the subpial layer in both DS patients and controls suggesting the functioning role of APP as a growth factor. This immunoreactivity disappeared in childhood and reappeared in adulthood in only DS patients. The earlier reappearance of those in DS patients from a young adult age than in normal controls may result from a gene dosage effect, since APP is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in glial cells in the developing white matter in the both DS patients and controls may be associated with myelination glia. Immunoreactivity for KPI was noted on the tunica media of the arteries from the neonatal period to adulthood in only DS patients. In senile plaques in DS patients, N-terminal and Affi28 immunoreactivity became detectable at the age of 32 years. N-terminal immunoreactivity in the senile plaques was noted along the periphery of the senile plaques, while that for Affi28 was around the amyloid core. Thus, each fragment of APP exhibited a different localization and time course of immunohistochemical expression. The results indicated that APP plays a role in neuronal development and that its earlier reappearance in adult DS patients is associated with the regeneration process related to aging.
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- Abnormal neuronal development in the visual cortex of the human fetus and infant with Downs syndrome. A quantitative and qualitative Golgi study.Brain Res. 1981; 225: 1-21
- Amyloid plaque core protein in Alzheimer disease and Down syndrome.in: 3rd edition. Proc. Natl. Acad. Sci. USA. 82. 1985: 8729-8732
- The precursor of Alzheimer's disease amyloid A4 protein resembles a cellsurface receptor.Nature. 1987; 325: 733-736
- The molecular pathology of Alzheimer's disease.Neuron. 1991; 6: 487-498
- Expression of β-amyloid precursor protein in axons of periventricular leukomalacia brains.Pediatr. Neurol. 1995; 13: 161-163
- Developmental changes of apolipoprotein E immunoreactivity in Down syndrome brains.Dev. Brain Res. 1995; 87: 228-233
- Conventional protein kinase C (PKC)-α and novel PKC ε, but not -δ, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts.FEBS Lett. 1995; 364: 203-206
- High expression on Kunitz-type protease inhibitor-containing substances in the cerebral vessels of patients with Down syndrome.Tohoku J. Exp. Med. 1994; 174: 181-187
- Developmental and aging changes in the expression patterns of beta-amyloid in the brains of normal and Down's syndrome cases.Brain Dev. 1990; 12: 367-371
- Dendritic and histochemical development and ageing in patients with Downs syndrome.J. Intellect. Disab. Res. 1994; 38: 265-273
- Potentially amyloidogenic, car☐yl-terminal derivatives of the amyloid protein precursor.Science. 1992; 255: 726-728
- Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein.Neuron. 1993; 10: 243-254
- Developmental changes of glial fibrillary acidic protein in the cerebral white matter.Arch. Neurol. 1983; 40: 14-18
- Precursor of amyloid protein in Alzheimer's disease undergoes fast anterograde axonal transport.in: 3rd edition. Proc. Natl. Acad. Sci. USA. 87. 1990: 1561-1565
- Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions.Neurosci. Lett. 1992; 136: 75-78
Accepted: November 1, 1996
Received: May 14, 1996
© 1997 Elsevier Science B.V. All rights reserved. Published by Elsevier Inc.