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A single mutation in the human GRN gene resulting in reduced PGRN expression causes types of frontotemporal lobar degeneration resulting in frontotemporal dementia. Prosaposin (PSAP) is also a multifunctional neuroprotective secreted protein and regulator of lysosomal function. Interactions of PGRN and PSAP affect their functional properties. Their roles in Alzheimer\u2019s disease (AD), the leading cause of dementia, have not been defined. In this report, we examined in detail the cellular expression of PGRN in middle temporal gyrus samples of a series of human brain cases (<jats:italic>n<\/jats:italic>\u00a0=\u200945) staged for increasing plaque pathology. Immunohistochemistry showed PGRN expression in cortical neurons, microglia, cerebral vessels and amyloid beta (A\u03b2) plaques, while PSAP expression was mainly detected in neurons and A\u03b2 plaques, and to a limited extent in astrocytes. We showed that there were increased levels of PGRN protein in AD cases and corresponding increased levels of PSAP. Levels of PGRN and PSAP protein positively correlated with amyloid beta (A\u03b2), with PGRN levels correlating with phosphorylated tau (serine 205) levels in these samples. Although PGRN colocalized with lysosomal-associated membrane protein-1 in neurons, most PGRN associated with A\u03b2 plaques did not. A\u03b2 plaques with PGRN and PSAP deposits were identified in the low plaque non-demented cases suggesting this was an early event in plaque formation. We did not observe PGRN-positive neurofibrillary tangles. Co-immunoprecipitation studies of PGRN from brain samples identified only PSAP associated with PGRN, not sortilin or other known PGRN-binding proteins, under conditions used. Most PGRN associated with A\u03b2 plaques were immunoreactive for PSAP showing a high degree of colocalization of these proteins that did not change between disease groups. As PGRN supplementation has been considered as a therapeutic approach for AD, the possible involvement of PGRN and PSAP interactions in AD pathology needs to be further considered.<\/jats:p>","DOI":"10.1186\/s40478-019-0862-8","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T12:02:29Z","timestamp":1576929749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer\u2019s disease and aged brains: increased levels correlate with neuropathology"],"prefix":"10.1186","volume":"7","author":[{"given":"Anarmaa","family":"Mendsaikhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Tooyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Bellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia I.","family":"Sue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lih-Fen","family":"Lue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5126-7926","authenticated-orcid":false,"given":"Douglas G.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"862_CR1","unstructured":"(2016) World Alzheimer Report 2016. http:\/\/www.alz.co.uk\/research\/WorldAlzheimerReport2016.pdf"},{"key":"862_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure MA, Dickson DW (2019) The neuropathological diagnosis of Alzheimer\u2019s disease. 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The operation of the BBDP in terms of collecting clinical data has been continuously approved since initiation. Current approval was carried out by Western IRB (Puyallup, WA). The consenting form for tissue donation allows the sharing of tissue with qualified researchers in research projects. The use of anonymized human tissue for research in the U.S.A. is not considered human subject research under Federal regulations exemption 4 (C.F.R 46.101). Most of the tissue samples described in this study were transferred to Japan when DGW moved institution, under a material transfer agreement (MTA) between Banner Health and Shiga University of Medical Science. Tissue studies carried out in Japan are considered human research with these studies being approved by Shiga University of Medical Science Ethical Committee (Certificate no. 29\u2013114). The identifiable information on each subject is not known to personnel carrying out the research in this report (AM, IT, JPB, LFL and DGW).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All listed authors have reviewed the completed manuscript and have consented to publication of this report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Authors report no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"215"}}