en Cell, Stem Cell and Cancer Cell, Stem Cell and Cancer Experimental research article Experimental research article <strong>Introduction: </strong>Alzheimer&rsquo;s disease (AD) is an age-related disorder, characterized by the gradual loss of memory and cognitive function owing to neuronal damage and brain shrinkage. This study aimed to investigate how intranasal injection of human adipose-derived stem cell-conditioned media (hADSC-CM) ameliorates cognitive performance and affects the level of estrogen receptor beta (Er&beta;) in the hippocampus of rats in an AD model.<br /> <strong>Methods: </strong>A total of 32 male rats were divided into four groups, including the control, AD model, hADSC-CM, and vehicle groups. The Morris water maze was used to assess the animals&rsquo; behavioral changes. Moreover, Nissl and Thioflavin-S staining were performed to evaluate the histology of the hippocampus. Immunohistochemistry was also carried out to evaluate the expression level of Er&beta;.&nbsp;<br /> <strong>Results: </strong>The intranasal injection of hADSC-CM improved the rats&rsquo; cognitive performance by reducing the number of dark cells and beta-amyloid plaques in the hippocampus in the AD model. Besides, the intranasal injection of hADSC-CM increased the level of Er&beta; in this model.<br /> <strong>Conclusion:</strong> The present findings indicated that the intranasal injection of hADSC-CM ameliorated cognitive function. Amyloid plaques and dark cells also diminished in the CA1 area of the hippocampus. Moreover, the expression level of ER&beta; increased. It can be concluded that hADSC-CM has significant treatment benefits for AD in rats. Alzheimer’s Disease, Estrogen receptors, Human adipose-drive stem, Cell therapy, Cognitive performance 43 55 http://ppj.phypha.ir/browse.php?a_code=A-10-2085-1&slc_lang=en&sid=1 Seyed Amir shaker 72shaker@gmail.com 3200319475328460034166 0000000232857936 No Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Houman Parsaei houman70parsaie@yahoo.com 3200319475328460034167 0000000218208913 No Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, IranDepartment of Anatomy, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Naser amini amini_ot@yahoo.com 3200319475328460034168 0000000184539342 No Neuroscience Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Maliheh Nobakht nobakht.m@iums.ac.ir 3200319475328460034169 0000000323526331 No Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Javad fahanik babaei j-fbabaei@farabi.tums.ac.ir 3200319475328460034170 000000016707132X No Electrophysiology Research Center, Tehran University of Medical Science, Tehran, Iran Ali Dadseresht dadseresht.a@iums.ac.ir 3200319475328460034171 0000000205615405 No Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Elham Seidkhani seidkhani.e@iums.ac.ir 3200319475328460034172 0000000221908910 No Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mina Eftekharzadeh eftekhar.zade@yahoo.com 3200319475328460034173 0000000340889070 Yes Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran