Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.

Abstract

The protein component of Alzheimer's disease amyloid [neurofibrillary tangles (NFT), amyloid plaque core and congophilic angiopathy] is an aggregated polypeptide with a subunit mass of 4 kd (the A4 monomer). Based on the degree of N‐terminal heterogeneity, the amyloid is first deposited in the neuron, and later in the extracellular space. Using antisera raised against synthetic peptides, we show that the N terminus of A4 (residues 1‐11) contains an epitope for neurofibrillary tangles, and the inner region of the molecule (residues 11‐23) contains an epitope for plaque cores and vascular amyloid. The non‐protein component of the amyloid (aluminum silicate) may form the basis for the deposition or amplification (possible self‐replication) of the aggregated amyloid protein. The amyloid of Alzheimer's disease is similar in subunit size, composition but not sequence to the scrapie‐associated fibril and its constituent polypeptides. The sequence and composition of NFT are not homologous to those of any of the known components of normal neurofilaments.

Metalloenzyme-like Activity of Alzheimer's Disease β-Amyloid

“…A␤1-40 is the major soluble species (1), and A␤1-42 is a minor species but is enriched in plaque amyloid (2). Familial ADlinked mutations of amyloid protein precursor, presenilin-1 and presenilin-2, increase the concentration of A␤1-42 (3).…”

Peroxidase Activity of Cyclooxygenase-2 (COX-2) Cross-links β-Amyloid (Aβ) and Generates Aβ-COX-2 Hetero-oligomers That Are Increased in Alzheimer's Disease

“…There is already abundant evidence for SDS-resistant A␤ dimers and polymers being enriched in AD-affected post-mortem brain tissue (2,30). Furthermore, there is evidence of elevated H 2 O 2 in AD-affected brain tissue (4).…”

Neurofibrillary Tangles of Aβx-40 in Alzheimer’s Disease Brains

“…The existence of intraneuronal A␤ has been known for many years. Masters and collaborators published in 1985 that A␤, initially termed amyloid A4, is deposited first intraneuronally as NFT and subsequently in the extracellular space, associated with senile plaques and blood vessels [5]. Later on, the immunolabeling of most intraneuronal NFT (iNFT) and extraneuronal NFT (eNFT) with anti-A␤ antibodies was replicated in several laboratories [6][7][8] However, other studies failed to find A␤ immunolabeling associated with iNFT [9][10][11] or with both iNFT and eNFT [12].…”