Animal Models for Neurological Disorders

Accelerating Alzheimer’s Disease Research by Pharmacologic, Genetic, and Computational Based Animal Models

Author(s): Monika Kadian, Nitin Rawat, Hemprabha Tainguriya and Anil Kumar * .

Pp: 1-51 (51)

DOI: 10.2174/9789815039689121010004

* (Excluding Mailing and Handling)

Abstract

Alzheimer’s disease (AD) is a type of dementia characterized pathologically by inappropriate neuronal loss in the specific brain regions, mainly in the hippocampus and cerebral cortex, where an accumulation of insoluble plaques of amyloid-beta (Aβ) and tau tangles formation occurs, resulting in progressive memory loss, impaired thinking, deterioration and changes in personality and mood. Alzheimer’s disease now possesses a significant health burden and is considered the main source of inability among aged individuals. Recently, Alzheimer's Disease International (ADI) evaluations of 2019 featured that there would be more than 50 million individuals living with dementia around the world, a figure set to increment to 152 million by 2050. Somebody creates dementia-like clockwork, and the current year expense of dementia is assessed at US $1trillion, a figure set to twofold by 2030. AD is the leading cause of dementia and accounts for 60-80% of cases. In spite of the fact that Aβ conglomeration and neurofibrillary tangles (NFTs) development are notable major causative components engaged with AD pathogenesis, the researchers failed to cure or prevent progression of disease effectively by focusing on these pathogenic variables. Thus, tackling AD is a complex job, as we have erudite lately by continuous phase III clinical trial programs failures. Due to the lack of a clear etiology and increased morbidity associated with Alzheimer's disease, there is an immediate need to investigate the underlying causes of the disease and design and develop novel therapeutic agents to slow or reverse disease progression. Animal models mimicking different types of ADlike pathological conditions, which is an essential component in discovering potential therapeutic targets and studying mechanism of action behind that therapeutic agent, as we know, are primary tools in the field of biomedical research including AD. This chapter discusses emerging pathophysiological mechanisms and drug targets, as well as a summary of in-vivo/ex-vivo, in-vitro, QSAR, and in-silico models commonly used in Alzheimer's disease research. Moreover, we will also describe how to select suitable and valid models and the specifications and relevance of a couple of behavioral assessment methods.


Keywords: Alzheimer’s disease, Behavioral animal models, In-silico models, Therapeutic strategies, Transgenic animal models.

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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 <= 51739267 and j.to_ip >=51739267 )) and ((j.from_date <= 1739988770 and j.to_date >= 1739988770 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16113) 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 <= 51739267 and j.to_ip >=51739267 )) and ((j.from_date <= 1739988770 and j.to_date >= 1739988770 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16113) 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 <= 51739267 and j.to_ip >=51739267 )) and ((j.from_date <= 1739988770 and j.to_date >= 1739988770 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16113)
      610μsalphaeurekaselec_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` = 3280 and `b`.`banner_from_date` <= 1739988770 and `b`.`banner_to_date` >= 1739988770 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.48msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3280
      • 3: 1739988770
      • 4: 1739988770
      • 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='fde6f08dca19a0009700dd7c662096af'
      260μsalphaeurekaselec_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\Keywords
    5Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        lJD0QpbcoHHuUztt2B7HivTxo1Qf2Rvt8CYUWwBV
        uc_cart_id
        fde6f08dca19a0009700dd7c662096af
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/16113" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16113
        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
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        session_attributes
        0 of 0
        array:5 [ "_token" => "lJD0QpbcoHHuUztt2B7HivTxo1Qf2Rvt8CYUWwBV" "uc_cart_id" => "fde6f08dca19a0009700dd7c662096af" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/16113" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:12:50GET/chapter/16113112197