{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:51:13Z","timestamp":1773730273403,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,9]],"date-time":"2004-10-09T00:00:00Z","timestamp":1097280000000},"content-version":"vor","delay-in-days":4080,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[1993,8,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunocytochemical techniques were employed to examine the temporal ordering whereby amyloid \u03b2\u2010protein (A\u03b2P) and neuronal elements collectively come together to form senile plaques in Alzheimer's disease (AD). Specifically, we addressed three questions: (1) whether A\u03b2P deposition precedes or follows neuritic changes; (2) whether paired helical filament (PHF) formation is an early or late event in the genesis of the dystrophic neurites which participate in plaque formation; and (3) whether the density of senile plaques displays any relationship with the prevalence of PHF or Alz\u201050 containing neurons. To address these questions we studied the amygdala from a group of patients with AD, a group of nondemented age\u2010matched individuals exhibiting a sufficient number of senile plaques to be classified by neuropathological criteria as AD, and a group of age\u2010matched controls without AD pathology. Amyloid\u2010bearing plaques were demonstrated by A\u03b2P immunolabeling and thioflavine\u2010S staining. Neuritic changes in the form of dystrophic neurites were observed with the aid of antibodies against PHF, Alz\u201050, as well as antibodies against several neuropeptides (i.e., substance P, somatostatin, and neurotensin) and the acetylcholine biosynthetic enzyme, choline acetyltransferase.<\/jats:p><jats:p>By using a graded range of pathologic changes both within and across the patient population to provide us with a means of evaluating plaque deposition from its earliest to most advanced stages of development, we observed in patients and\/or regions of the amygdala displaying a mild degree of pathologic change A\u03b2P deposition in the absence of any neuritic changes. With increasing density of A\u03b2P, however, we began to observe dystrophic neurites within plaques. In regions of relatively few plaques, the dystrophic neurites were immunolabeled only with antibodies against the various neurotransmitters and they lacked evidence of cytoskeletal pathology (i.e., Alz\u201050 or PHF). Only as the density of A\u03b2P increased further within a region, were dystrophic neurites observed that exhibited Alz\u201050 or PHF. In no instance did we observe a relationship between the density of A\u03b2P deposition and the density of Alz\u201050 or PHF\u2010immunoreactive neurons. Collectively, our data suggest that the deposition of A\u03b2P is an early pathologic event in senile plaque formation. Thereafter, swollen neurites can be seen in the vicinity of A\u03b2P. This early neuritic response, which can first be visualized by immunolabeling for one or another transmitter substance, is followed by alterations in the cytoskeleton as recognized initially by antibodies to Alz\u201050 and subsequently by the presence of PHF. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.903340203","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T08:56:44Z","timestamp":1104569804000},"page":"176-191","source":"Crossref","is-referenced-by-count":39,"title":["Evidence that transmitter\u2010containing dystrophic neurites precede paired helical filament and Alz\u201050 formation within senile plaques in the amygdala of nondemented elderly and patients with Alzheimer's disease"],"prefix":"10.1002","volume":"334","author":[{"given":"William C.","family":"Benzing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milos D.","family":"Ikonomovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel R.","family":"Brady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1989.tb01252.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(86)90564-1"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(88)80051-4"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90431-4"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91396-6"},{"key":"e_1_2_1_7_1","first-page":"551","article-title":"Alzheimer\u2010type neuropathology and clinical symptoms of dementia in mentally retarded people without Down syndrome","volume":"93","author":"Barcikowska M.","year":"1989","journal-title":"Am. J. Ment. Retard."},{"key":"e_1_2_1_8_1","first-page":"163","volume-title":"The Amygdaloid Complex","author":"Ben\u2010Ari Y.","year":"1981"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-111-6-2149"},{"key":"e_1_2_1_10_1","first-page":"949","article-title":"Morphological alterations of neuropeptides in the amygdala in Alzheimer's disease","volume":"20","author":"Benzing W. C.","year":"1990","journal-title":"Neurosci. Abst."},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90372-I"},{"key":"e_1_2_1_12_1","first-page":"352","article-title":"Transmitter specific abnormal neurites are present in amyloid positive plaques prior to the appearance of paired helical filament containing processes","volume":"17","author":"Benzing W. C.","year":"1991","journal-title":"Soc. Neurosci. 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