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Characterization of newly synthesized beta-amyloid precursor protein in rat and human
8A
BIOL PSYCHIATRY 1989;25:illA-119A
Alzheimer’s
Disease
Lewy bodies have been a concomitant finding in approximately 20% of cases diagnosed with Alzheimer’s disease (AD) by current neuropathologic criteria. In a series of 57 AD cases evaluated using the CERAD neuropathologic assessment procedure, 13 (24.7%) demonstrated Lewy bodies in the substantia nigra, nucleus basalis or locus coeruleus. The extent of neocortical plaque and neurofibrillary tangle formation was evaluated in the Lewy body positive and negative cases. Plaques and tangles were scored (0 = none, 1 = sparse, 3 = moderate, 5 = frequent) according to CERAD specifications. Significantly fewer neurofibrillary tangles were present in the Lewy body positive cases in the mid-frontal (t = 2.28, p = .026), superior temporal (t = 3.35, p = .OOl), and inferior parietal cortices (t = 2.35, p = .023), whereas the extent of plaque formation did not differ between the groups. Cortical concentrations of HVA and CAT activity were assessed in a sub-sample of six Lewy body positive and 14 Lewy body negative cases; no group differences, however, were noted. These data suggest that the extent of cortical neurofibrillary tangle formation in AD may be associated with the subcortical expression of Lewy bodies.
239 CHARACTERIZATION OF NEWLY SYNTHESIZED BETAAMYLOID PRECURSOR PROTEIN IN RAT AND HUMAN William Wallace, Mani Krishnamurthi, Jason Gotlib, Lawrence Refolo, Vahram Haroutunian, Nikolaos K. Robakis New York, NY
The beta-amyloid peptide, which is the primary constituent of the senile plaques that occur in Alzheimer’s disease, derives post-translationally from a larger polypeptide termed the beta-amyloid precursor protein (APP) .The APP gene can make three distinct mRNA species (A695, A751, and A770). We have used polysomes isolated from brain to identify and characterize the newly synthesized form of APP in the absence of any post-translational modifications. Human polysomes synthesize at least two distinct forms of the APP in approximately equal amounts. The larger APP species (120 kD) is the product of the A75 1 mRNA while the smaller species (110 kD) is a product of the A695 mRNA. Both APPs are synthesized by membrane-bound polysomes and exhibit a microheterogeneity that is modified by the presence of dog pancreas microsomes during their synthesis. Interestingly, the rat polysomes synthesize very little of the 120 kD species and dog polysomes synthesize intermediate levels. Thus, the synthesis of the large APP correlates with those animal species which can form senile plaques. Co-translational or post translational modiftcations of the 120 kD APP may be involved in the biogenesis of senile plaques during Alzheimer’s disease.
240 EXPRESSION OF BETA-AMYLOID PRECURSOR NEURON PLASMA MEMBRANES Larry D. Altstiel, Nikolaos K. Robakis
PROTEIN ON
New York, NY
The beta-amyloid peptide is the major constituent of the senile plaques found in the brains of patients with Alzheimer’s disease. Beta-peptide is derived from a larger precursor protein, beta-amyloid precursor protein (APP). The amino acid sequence of
BIOL PSYCHIATRY 1989;25:illA-119A
Alzheimer’s
Disease
Lewy bodies have been a concomitant finding in approximately 20% of cases diagnosed with Alzheimer’s disease (AD) by current neuropathologic criteria. In a series of 57 AD cases evaluated using the CERAD neuropathologic assessment procedure, 13 (24.7%) demonstrated Lewy bodies in the substantia nigra, nucleus basalis or locus coeruleus. The extent of neocortical plaque and neurofibrillary tangle formation was evaluated in the Lewy body positive and negative cases. Plaques and tangles were scored (0 = none, 1 = sparse, 3 = moderate, 5 = frequent) according to CERAD specifications. Significantly fewer neurofibrillary tangles were present in the Lewy body positive cases in the mid-frontal (t = 2.28, p = .026), superior temporal (t = 3.35, p = .OOl), and inferior parietal cortices (t = 2.35, p = .023), whereas the extent of plaque formation did not differ between the groups. Cortical concentrations of HVA and CAT activity were assessed in a sub-sample of six Lewy body positive and 14 Lewy body negative cases; no group differences, however, were noted. These data suggest that the extent of cortical neurofibrillary tangle formation in AD may be associated with the subcortical expression of Lewy bodies.
239 CHARACTERIZATION OF NEWLY SYNTHESIZED BETAAMYLOID PRECURSOR PROTEIN IN RAT AND HUMAN William Wallace, Mani Krishnamurthi, Jason Gotlib, Lawrence Refolo, Vahram Haroutunian, Nikolaos K. Robakis New York, NY
The beta-amyloid peptide, which is the primary constituent of the senile plaques that occur in Alzheimer’s disease, derives post-translationally from a larger polypeptide termed the beta-amyloid precursor protein (APP) .The APP gene can make three distinct mRNA species (A695, A751, and A770). We have used polysomes isolated from brain to identify and characterize the newly synthesized form of APP in the absence of any post-translational modifications. Human polysomes synthesize at least two distinct forms of the APP in approximately equal amounts. The larger APP species (120 kD) is the product of the A75 1 mRNA while the smaller species (110 kD) is a product of the A695 mRNA. Both APPs are synthesized by membrane-bound polysomes and exhibit a microheterogeneity that is modified by the presence of dog pancreas microsomes during their synthesis. Interestingly, the rat polysomes synthesize very little of the 120 kD species and dog polysomes synthesize intermediate levels. Thus, the synthesis of the large APP correlates with those animal species which can form senile plaques. Co-translational or post translational modiftcations of the 120 kD APP may be involved in the biogenesis of senile plaques during Alzheimer’s disease.
240 EXPRESSION OF BETA-AMYLOID PRECURSOR NEURON PLASMA MEMBRANES Larry D. Altstiel, Nikolaos K. Robakis
PROTEIN ON
New York, NY
The beta-amyloid peptide is the major constituent of the senile plaques found in the brains of patients with Alzheimer’s disease. Beta-peptide is derived from a larger precursor protein, beta-amyloid precursor protein (APP). The amino acid sequence of