Frontiers in Clinical Drug Research - Alzheimer Disorders

Volume: 5

Recent Perspective About the Amyloid Cascade Hypothesis and Stem Cell-Based Therapy in the Treatment of Alzheimer's Disease

Author(s): Hany E. Marei, Asmaa Althani, Jaana Suhonen, Mohamed E. El Zowalaty, Mohammad A. Albanna, Carlo Cenciarelli, Tengfei Wang and Thomas Caceci

Pp: 144-174 (31)

DOI: 10.2174/9781681082318116050006

* (Excluding Mailing and Handling)

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative condition that is clinically characterized by impaired cognitive functions. The major morphologically observed lesion of AD encompasses the accumulation of extracellular amyloid aggregates (plaques) formed of amyloid-β (Aβ) protein and of intracellular neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein. According to the currently accepted amyloid cascade hypothesis, the major induction factor underlying the loss of cholinergic neurons in the cortex and hippocampus is the pathological accumulation of a smaller protein fragments known as amyloid-β which in turn is derived from a larger membrane protein called amyloid precursor protein (APP). Based on this hypothesis, several diagnostic and drug-based therapeutic interventions were suggested, mostly targeting amyloid-β and hyperphosphorylated Tau proteins. Several data have emerged that might indicate the inconsistency of the amyloid cascade hypothesis. Moreover, due to the purely palliative nature of AD drugs used so far, new stem cell-based therapy has been suggested as a promising potential therapeutic approach. Several cell sources have been used, such as embryonic stem cells, neural stem cells, mesenchymal stem cells, and induced pluripotent stem cells. While this suite of cell-based trials has shown promising results in preclinical paradigms, stumbling blocks still exist in the current treatment regimens. The present review highlights the recent perspective that argues against the long standing amyloid cascade hypothesis as well as the major efforts in the experimental application of stem cellbased therapies used as treatment options for AD, and discusses the major impediments against their successful translation into clinical.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59226591 and j.to_ip >=59226591 )) and ((j.from_date <= 1740422112 and j.to_date >= 1740422112 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9189) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59226591 and j.to_ip >=59226591 )) and ((j.from_date <= 1740422112 and j.to_date >= 1740422112 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9189) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59226591 and j.to_ip >=59226591 )) and ((j.from_date <= 1740422112 and j.to_date >= 1740422112 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9189)
      510μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1985 and `b`.`banner_from_date` <= 1740422112 and `b`.`banner_to_date` >= 1740422112 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1985
      • 3: 1740422112
      • 4: 1740422112
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='b6cbd757008f41d03a66df9b16562550'
      190μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        MxiqadQA3RVOsU7WN2FIeM3aS8dj66bwBXMH8ccV
        uc_cart_id
        b6cbd757008f41d03a66df9b16562550
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/9189" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/9189
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 24 Feb 2025 18:35:12 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Inl4SzFvT1ZIQzRIMlpmZVp0dGJsQUE9PSIsInZhbHVlIjoiS3JWOEJGM2tOMHRiY3B2ZjVwUTFMSmc4dThIbGZabVo1Q2FwaEYvWmpFODVyN0d0UzB2T3l0UUo1dlBCZVl0bHo4bTVMSWxLdXMwdUNqc1BVZDBQSWR5dWVKV2xiMndVUHdIcmx5SFZmdncvRm9QVzFtZDhSK1g2RjBaVE9EQ1EiLCJtYWMiOiI1NmRiOTE0YmVmMzVkOTkwZDcyYTJkZTM2ZWJlODVhOGNkOTc2NGFmOTBkNjJhOGNiMDY0NzY1NTJhY2M1MDkzIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 06:35:12 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Inl4SzFvT1ZIQzRIMlpmZVp0dGJsQUE9PSIsInZhbHVlIjoiS3JWOEJGM2tOMHRiY3B2ZjVwUTFMSmc4dThIbGZabVo1Q2FwaEYvWmpFODVyN0d0UzB2T3l0UUo1dlBCZVl0bHo4bTVMS" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjRBaldWKzh6ZEg1S3lyc3plL3ZuQ1E9PSIsInZhbHVlIjoiVEQ3dGp5MUlNMW5oVFZ2UEVrM2w2b0w5clMzRTN2ZzNEamhVU25jTGlEdjlmOWRJcFpiWkRTcW8wcGVacTFjNjk5T01IMlRoYjdvamFsaHF5MG9tVjUzbzM3NkdldGtISVlwcWdWM2U3NEFObEI0eUxPWU11WU5NWmV6dFgyTDciLCJtYWMiOiJiYjdjZWMzMWUxNTEwNzQyNDA3NzYzOTY5YTk3ODVlZTU0MTRjODVlNzA2ZGVlMTBiMzMzM2U2ZDQyZmY2N2I0IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjRBaldWKzh6ZEg1S3lyc3plL3ZuQ1E9PSIsInZhbHVlIjoiVEQ3dGp5MUlNMW5oVFZ2UEVrM2w2b0w5clMzRTN2ZzNEamhVU25jTGlEdjlmOWRJcFpiWkRTcW8" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Inl4SzFvT1ZIQzRIMlpmZVp0dGJsQUE9PSIsInZhbHVlIjoiS3JWOEJGM2tOMHRiY3B2ZjVwUTFMSmc4dThIbGZabVo1Q2FwaEYvWmpFODVyN0d0UzB2T3l0UUo1dlBCZVl0bHo4bTVMSWxLdXMwdUNqc1BVZDBQSWR5dWVKV2xiMndVUHdIcmx5SFZmdncvRm9QVzFtZDhSK1g2RjBaVE9EQ1EiLCJtYWMiOiI1NmRiOTE0YmVmMzVkOTkwZDcyYTJkZTM2ZWJlODVhOGNkOTc2NGFmOTBkNjJhOGNiMDY0NzY1NTJhY2M1MDkzIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 06:35:12 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Inl4SzFvT1ZIQzRIMlpmZVp0dGJsQUE9PSIsInZhbHVlIjoiS3JWOEJGM2tOMHRiY3B2ZjVwUTFMSmc4dThIbGZabVo1Q2FwaEYvWmpFODVyN0d0UzB2T3l0UUo1dlBCZVl0bHo4bTVMS" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjRBaldWKzh6ZEg1S3lyc3plL3ZuQ1E9PSIsInZhbHVlIjoiVEQ3dGp5MUlNMW5oVFZ2UEVrM2w2b0w5clMzRTN2ZzNEamhVU25jTGlEdjlmOWRJcFpiWkRTcW8wcGVacTFjNjk5T01IMlRoYjdvamFsaHF5MG9tVjUzbzM3NkdldGtISVlwcWdWM2U3NEFObEI0eUxPWU11WU5NWmV6dFgyTDciLCJtYWMiOiJiYjdjZWMzMWUxNTEwNzQyNDA3NzYzOTY5YTk3ODVlZTU0MTRjODVlNzA2ZGVlMTBiMzMzM2U2ZDQyZmY2N2I0IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjRBaldWKzh6ZEg1S3lyc3plL3ZuQ1E9PSIsInZhbHVlIjoiVEQ3dGp5MUlNMW5oVFZ2UEVrM2w2b0w5clMzRTN2ZzNEamhVU25jTGlEdjlmOWRJcFpiWkRTcW8" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "MxiqadQA3RVOsU7WN2FIeM3aS8dj66bwBXMH8ccV" "uc_cart_id" => "b6cbd757008f41d03a66df9b16562550" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/9189" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-24 18:35:12GET/chapter/9189112193