Advances in Alzheimer's Research

Volume: 2

Detection and Quantitation of Amyloid-β Aggregates in Body Fluids may be Suitable for Early Diagnosis of Alzheimer’s Disease

Author(s): Susanne A. Funke, Eva Birkmann and Dieter Willbold

Pp: 275-290 (16)

DOI: 10.2174/9781608058525114020013

* (Excluding Mailing and Handling)

Abstract

The post mortem identification of amyloid plaques, consisting of the amyloid-β (Aβ) peptide, and neurofibrillary tangles in the brains of patients still leads to the most reliable diagnosis for Alzheimer’s disease (AD). Substantial efforts have been made to identify reliable biomarkers for AD that can be used for early diagnosis of AD. Body fluids of AD patients have been investigated for their content of total or soluble Aβ(1-40) or Aβ(1-42), either using classical ELISA procedures, or non-classical assays with more innovative read-out signals, or a combination of both. The concentration of total soluble Aβ(1-42) in cerebrospinal fluid (CSF) is reduced by 40 to 50 % in AD patients compared to age-matched healthy controls, as confirmed in more than 30 studies, with both sensitivity and specificity exceeding 80 to 90 %. Thus, it was suggested that detection of low levels of Aβ(1-42) in CSF might help preclinical diagnosis. The achievable sensitivity using such CSF biomarkers, however, is 85 % or less. Therefore, these assays cannot deliver any increase in the diagnostic outcome as compared to existing algorithms based on neuropsychological and imaging modalities. Regarding the amyloid cascade hypothesis, Aβ oligomers and aggregates are directly involved in the pathologic process. The presence of Aβ aggregates in CSF could thus be the most direct and most reliable biomarker for AD and increasing efforts are undertaken to develop methods that are suitable to quantify and characterize Aβ aggregate species present in body fluids, especially in CSF. Here, we present an overview of the current status of the development of methods for Aβ aggregate specific detection and quantitation, which is an update of a previous review.


Keywords: Alzheimer’s disease, amyloid-β aggregates, biomarker, early diagnosis, prognosis, protein misfolding diseases, therapy monitoring.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 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 <= 316522063 and j.to_ip >=316522063 )) and ((j.from_date <= 1739834611 and j.to_date >= 1739834611 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6728) 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 <= 316522063 and j.to_ip >=316522063 )) and ((j.from_date <= 1739834611 and j.to_date >= 1739834611 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6728) 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 <= 316522063 and j.to_ip >=316522063 )) and ((j.from_date <= 1739834611 and j.to_date >= 1739834611 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6728)
      920μsalphaeurekaselec_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` = 1532 and `b`.`banner_from_date` <= 1739834611 and `b`.`banner_to_date` >= 1739834611 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.45msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1532
      • 3: 1739834611
      • 4: 1739834611
      • 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='54275dd44336f3a2506df8043ab7388e'
      250μsalphaeurekaselec_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
    7Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        eV4vxPinQDUyg330UUVT9tFkc20TvSwjqP1btzyG
        uc_cart_id
        54275dd44336f3a2506df8043ab7388e
        _previous
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        _flash
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        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
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        format
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        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:23:31GET/chapter/6728112199